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MiPNet18.18 IOC77 + ([[Image:O2k-Workshops.png|left|130px|link=O2k-Workshops]] '''77th Oroboros O2k-Workshop on high-resolution respirometry and O2k-Fluorometry'''. Newport Beach, California, USA; 2013 June 13.)
MiPNet24.04 IOC140 Amsterdam NL + ([[Image:O2k-Workshops.png|right|130px|link=O2k-Workshops]] '''Pre-conference Oroboros O2k-Workshop on high-resolution respirometry (HRR)''' in cooperation with [[SHVM 2019 Amsterdam NL|SHVM Conference]]. Amsterdam, Netherlands, 2019 June 23.)
MiPNet07.02 IOC20 + ([[Image:O2k-Workshops.png|right|150px|O2k- … [[Image:O2k-Workshops.png|right|150px|O2k-Workshops|link=O2k-Workshops]]'''O2k-Workshop on high-resolution respirometry.''' Bari, Italy; 2002 February 28.:>> O2k-Workshop: [[Oroboros Events| Current dates]]:>> Product: [[Oroboros O2k]], [[Oroboros O2k-Catalogue | O2k-Catalogue]][[Oroboros O2k-Catalogue | O2k-Catalogue]])
Komlodi 2022 MitoFit + ([[Komlodi 2022 Abstract Bioblast]]: The pr … [[Komlodi 2022 Abstract Bioblast]]: The protonmotive force ''pmF'' establishes the link between electrical and chemical components of energy transformation and coupling in oxidative phosphorylation in the mitochondrial electron transfer system. The electrical part is corresponding to the mitochondrial membrane potential Δ''Ψ''mt and the chemical part is related to the transmembrane pH gradient ΔpH. Although the contribution of ΔpH to ''pmF'' is smaller than that of Δ''Ψ''mt, ΔpH plays an important role in mitochondrial transport processes and regulation of reactive oxygen species production. Separate measurement of Δ''Ψ''mt and ΔpH allows for calculation of ''pmF''. Methods for monitoring Δ''Ψ''mt such as fluorescence dyes are generally available, while determination of ΔpH is more challenging. In this review, we focus on the application of the fluorescence ratiometric method using the acetoxymethyl ester form of 2,7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF/AM) for real-time monitoring of the intramitochondrial pH in isolated mitochondria. Knowing the intra- and extramitochondrial pH allows for calculating the ΔpH. Application of specific ionophores such as nigericin or valinomycin, exerts the possibility to dissect the two components of the ''pmF'' in different directions. Furthermore, we tried to summarize those mitochondrial processes, such as production of reactive oxygen species, where the ΔpH has an important role.esses, such as production of reactive oxygen species, where the ΔpH has an important role.)
Itkis 2010 Abstract IOC60 + ([[Leigh syndrome]] is a case of mitochondr … [[Leigh syndrome]] is a case of mitochondrial disease frequently ascribed to mitochondrial respiratory deficiency in muscles and in a wide variety of tissues. The clinical manifestation of this disease is extremely heterogeneous. It depends on a severity of oxidative phosphorylation ([[OXPHOS]]) damage and on need of different organs and tissues in ATP. Very often in such cases it is difficult to predict a causative mutation.In our laboratory we perform mitochondrial genes sequence analysis (in nuclear and mitochondrial DNA) of patients with Leigh and Leigh-like disease to determine a mutation. But mostly these patients are classified to a group with mitochondrial disorders just by phenotype features, not correctly sometimes. Thus, it would be highly important for us to apply a [[high-resolution respirometry]] (HRR) measurement on muscle biopsy to prove a mitochondrial dysfunction as a cause of the disease. Also this approach can help to avoid a needless analysis on patients with intact mitochondria.Another potential application of HRR in our research is measurement of respiration in fibroblast cell cultures of patients with defined rare mutation. As nowadays there is not a unique drug for such patients, they are usually subjected to a symptomatic treatment of various substances. We plan to treat fibroblast with different agents (e.g. antioxidants) to find the most effective one for every mutation individually. Therefore the HRR approach will improve the quality of our investigation. improve the quality of our investigation.)
Itkis MiP2010 + ([[Leigh syndrome]], a case of mitochondria … [[Leigh syndrome]], a case of mitochondrial disease, is a subacute necrotising [[encephalomyopathy]] frequently ascribed to mitochondrial respiratory chain deficiency in muscles and in a wide variety of tissues [1]. Defects of mitochondrial function are genetically unique because the different components involved in this process are encoded by nuclear and mitochondrial genome. The clinical manifestation of this disease is extremely heterogeneous [2,3]. It depends on the severity of oxidative phosphorylation ([[OXPHOS]]) damage and on the ATP requirement of different organs and tissues. The aetiology of a mutation and a proportion of mutant [[mitochondrial DNA]] (mtDNA) in a cell define the severity of a disease. Thus, point mutations in mtDNA can lead to clinical polymorphism, affecting young and adult patients at any age [4]. Very often in such cases it is difficult to predict a causative mutation [5]. Last year in our laboratory we performed mtDNA sequence analysis in [[blood cell]]s of a small group of patients with Leigh-like phenotype and with excluded mutations in [[SURF1]] gene and common mutations in mtDNA (such as T8993C/G substitution). We identified a total four different substitutions in five patients. Among these, in two different families it was the same substitution (13094T>C, ND5 region) but in patients with unlike manifestation. In the third patient we have found a mutation 13513G>A (ND5), which is reported as a frequent cause of Leigh-like syndrome [1]. Also two unknown mutations (14441T>C in ND6 region and 8839G>C in ATP6) were found. However, here a supplementary investigation was required to prove these substitutions being pathogenic mutations but not rare polymorphisms [5,6].Nowadays, detection of mutations is usually limited to frequent mutations in nuclear genes (genes SURF1, NDUFV1, NDUFS4, NDUFS7, etc.) and common mutations in the mitochondrial DNA. However, mutations in other mtDNA regions can be an important cause of oxidative phosphorylation disease as well and contributes to clinical variability of Leigh syndrome. Thus, it is recommended to deploy an analysis of mtATP6, ND1-ND6 regions of mtDNA as a routine screening for mitochondrial disorders with Leigh (Leigh-like) phenotype, because very often there is no evidence of causative mutation, if frequent mutations are excluded.1. Chol M, Lebon S, Bénit P, Chretien D, de Lonlay P, Goldenberg A, Odent S, Hertz-Pannier L, Vincent-Delorme C, Cormier-Daire V, Rustin P, Rötig A, Munnich A (2003) The mitochondrial DNA G13513A MELAS mutation in the NADH dehydrogenase 5 gene is a frequent cause of Leigh-like syndrome with isolated Complex I deficiency. J. Med. Genet. 40: 188-191.2. Zeviani M, Di Donato S (2004) Mitochondrial disorders. Brain 127: 2153–2172.3. Scheffler IE (2001) A century of mitochondrial research: achievements and perspectives. Mitochondrion 1: 3-31.4. Chinnery PF (1993-2000) Mitochondrial Disorders Overview. GeneReviews [Internet]. 5. Chinnery PF, Howell N, Andrews RM, Turnbull DM (1999) Mitochondrial DNA analysis: polymorphisms and pathogenicity. J. Med. Genet. 36: 505-510. 6. Mitchell AL, Elson JL, Howell N, Taylor RW, Turnbull DM (2006) Sequence variation in mitochondrial Complex I genes: mutation or polymorphism? J. Med. Genet. 43: 175–179. mutation or polymorphism? J. Med. Genet. 43: 175–179.)
Brunmair 2004 Diabetes + ([[Metformin]] and thiazolidinediones (TZDs … [[Metformin]] and thiazolidinediones (TZDs) are believed to exert their antidiabetic effects via different mechanisms. As evidence suggests that both impair cell respiration ''in vitro'', this study compared their effects on mitochondrial functions. The activity of [[Complex I]] of the respiratory chain, which is known to be affected by metformin, was measured in tissue homogenates that contained disrupted mitochondria. In homogenates of skeletal muscle, metformin and TZDs reduced the activity of Complex I (30 mmol/L metformin, -15 +/- 2 %; 100 µmol/L rosiglitazone, -54 +/- 7; and 100 µmol/L pioglitazone, -12 +/- 4; ''P'' < 0.05 each). Inhibition of Complex I was confirmed by reduced State 3 respiration of isolated mitochondria consuming glutamate + malate as substrates for Complex I (30 mmol/L metformin, -77 +/- 1 %; 100 µmol/l rosiglitazone, -24 +/- 4; and 100 µmol/l pioglitazone, -18 +/- 5; ''P'' < 0.05 each), whereas respiration with succinate feeding into Complex II was unaffected. In line with inhibition of Complex I, 24-h exposure of isolated rat soleus muscle to metformin or TZDs reduced cell respiration and increased anaerobic glycolysis (glucose oxidation: 270 µmol/L metformin, -30 +/- 9 %; 9 µmol/L rosiglitazone, -25 +/- 8; and 9 µmol/L pioglitazone, -45 +/- 3; lactate release: 270 µmol/L metformin, +84 +/- 12; 9 µmol/L rosiglitazone, +38 +/- 6; and 9 µmol/L pioglitazone, +64 +/- 11; ''P'' < 0.05 each). As both metformin and TZDs inhibit Complex I activity and cell respiration ''in vitro'', similar mitochondrial actions could contribute to their antidiabetic effects.ons could contribute to their antidiabetic effects.)
Tretter 2013 Abstract MiP2013 + ([[Methylmalonic acid]] (Mma) is a common i … [[Methylmalonic acid]] (Mma) is a common intermediate in many catabolic processes. Its accumulation is associated with neurological symptoms. In methylmalonic acidemia mitochondrial dysfunction can be observed. In this study the effects of Mma were tested in isolated brain, heart and liver mitochondria. Oxygen consumption of isolated mitochondria was measured by Clark electrode, ATP synthesis was estimated by coupled enzyme assay, mitochondrial membrane potential was measured by safranin fluorescence. It was found that in the presence of Mma alpha-ketoglutarate (aKG) oxidation was significantly increased in isolated mitochondria. The oxidation of Mma is reflected in the increased ATP production and membrane hyperpolarization. This phenomenon could be explained by: (i) The mitochondrial transport of aKG was increased by Mma; (ii) The added Mma was itself activated and oxidized; (iii) alpha-ketoglutarate dehydrogenase (aKGDH) activity was increased by Mma. The effect of Mma on isolated aKGDH was tested and found that the enzyme activity was inhibited by Mma. Our results are in good agreement with that of Melo et al (2012). According to their interpretation the stimulating effect of Mma can be attributed to the stimulation of aKG transport. Our recent experiments however showed that this stimulation does not occur in liver mitochondria but it is pronounced in mitochondria isolated from the brain and heart, respectively. One of the differences between these types of mitochondria is that heart and brain are tissues able to oxidize ketone bodies. We interpret our results that a reaction analogous to the ketone body activation may activate methylmalonate to methylmalonyl-CoA. This reaction occurs in the heart and brain, but not in the liver mitochondria, respectively. This hypothesis is supported by the Mma-induced changes in P/O ratio. In brain and heart mitochondria in the presence of Mma, P/O ratio of aKG oxidation decreases. This finding is in agreement with the hypothesis that acetoacetate:succinyl-CoA transferase can transfer CoA and activates Mma to Mma-CoA.transfer CoA and activates Mma to Mma-CoA.)
Gnaiger 2010 Abstract MiP2010 + ([[MiP2010]] starts with a provocative title: Mitochondrial physiology – the many functions of the organism in our cells. It is a citation of MiP2005 [1] with subtle change.)
MiPNet08.10 MiP2003 + ([[Mitochondrial Physiology Society]])
MiPNet12.18 MiPsummer 2007 + ([[Mitochondrial Physiology Society|Mitochondrial Physiology Society]])
MiPNet09.14 Monte Rosa Expedition 2004 + ([[Monte Rosa]])
Moreno-Sanchez 2022 MitoFit + ([[Moreno-Sanchez 2022 Abstract Bioblast]]: … [[Moreno-Sanchez 2022 Abstract Bioblast]]:Glycolytic and respiratory fluxes were analyzed in cancer and non-cancer cells. The steady-state fluxes in energy metabolism were used to estimate the aerobic glycolytic and mitochondrial (oxidative phosphorylation, OxPhos) contributions to the cellular ATP supply. The rate of lactate production ― corrected for the fraction generated by glutaminolysis ― is proposed as the appropriate way to estimate glycolytic flux. In general, the glycolytic rates estimated for cancer cells are higher than those found in non-cancer cells, as originally observed by Otto Warburg. The rate of ROUTINE ''R'' cellular O2 consumption corrected for LEAK respiration ''L'' measured after inhibition by oligomycin (a specific, potent and permeable ATP synthase inhibitor) becomes the respiratory ''R-L'' net ROUTINE capacity, which is proposed as the appropriate way to estimate mitochondrial ATP synthesis-linked O2 flux or net OxPhos flux in living cells. Detecting non-negligible O2 consumption rates in cancer cells has revealed that the mitochondrial function is not impaired, as claimed by the Warburg effect. Furthermore, when calculating the relative contributions to cellular ATP supply, under a variety of environmental conditions and for several different types of cancer cells, it was found that OxPhos was the main ATP provider over glycolysis. Hence, OxPhos targeting can be successfully used to block in cancer cells ATP-dependent processes such as migration. These observations may guide the re-design of novel targeted therapies.ation. These observations may guide the re-design of novel targeted therapies.)
Vera Vives 2022 MitoFit + ([[Morosinotto 2022 Abstract Bioblast]] The … [[Morosinotto 2022 Abstract Bioblast]] The rate of oxygen evolution provides valuable information on the metabolic status and the photosynthetic performance of a cell, and it can be quantified by means of a photosynthesis-irradiance (PI) curve. Up to now, the construction of PI curves of unicellular organisms based on oxygen evolution has been difficult and time consuming due to the lack of sensitive instruments. Here we describe the set up of a reproducible method for constructing PI curves based on oxygen evolution using low amounts of sample in the microalga ''Nannochloropsis gaditana'', easily translable to other algal species. easily translable to other algal species.)
MiPNet07.07 O2k-NetworkInvitation + ([[O2k-Network|'''O2k-Network''']].)
Karavyraki 2022 MitoFit + ([[Porter 2022 Abstract Bioblast]]: In an e … [[Porter 2022 Abstract Bioblast]]: In an endeavour to understand the metabolic phenotype behind oral squamous cell carcinomas, we characterised the bioenergetic profile of a human tongue derived cancer cell line (SCC-4 cells) and compared this profile to a pre-cancerous dysplastic oral keratinocyte (DOK) cell line also derived from human tongue. The human SCC-4 cancer cells had greater mitochondrial densitydensity but lower mitochondrial O2 flow per cell than DOK cells. The lower oxygen consumption rate in SCC-4 cells can be partially explained by lower NADH-related enzymatic activity and lower mitochondrial Complex I activity when compared to pre-cancerous DOK cells. In addition, SCC-4 cells have greater extracellular acidification rate (an index of glycolytic flux) when compared to DOK cells. In addition, treatment with recombinant human IL-6 (rhIL-6), known to drive anoikis resistance in SCC-4 cells but not DOK cells, impairs oxygen consumption in SCC-4 but not DOK cells, without affecting mitochondrial density. We conclude that SCC-4 cells have a less oxidative phenotype compared to DOK cells and that IL-6 attenuates mitochondrial function in SCC-4 cells while increasing glycolytic flux.-4 cells while increasing glycolytic flux.)
Abed Rabbo 2022 MitoFit + ([[Stiban 2022 Abstract Bioblast]]: Mitocho … [[Stiban 2022 Abstract Bioblast]]: Mitochondrial ailments are diverse and devastating. Defects in mitochondrial DNA or its products lead to wide range of deficiencies in the mitochondrial electron transfer system and its ensuing energy production. Accessory proteins required for the assembly and function of the respiratory complexes are also required for healthy, coupled, and energy-producing mitochondria. Recently, the protein nucleotide binding protein like (NUBPL or IND1) was identified as an iron-sulfur cluster transfer protein specifically for Complex I. Since the presence of multiple iron-sulfur clusters in Complex I is necessary for its activity, deficiency in NUBPL leads to severely dysfunctional mitochondria, with upregulated compensatory Complex II activity. Here we present a short review of the debilitating disease related to NUBPL deficiency.ating disease related to NUBPL deficiency.)
Torres-Quesada 2022 MitoFit Kinase + ([[Torres-Quesada 2022 Abstract Bioblast]]: … [[Torres-Quesada 2022 Abstract Bioblast]]: Protein kinases take the center stage in numerous signaling pathways by phosphorylating compartmentalized protein substrates for controlling cell proliferation, cell cycle and metabolism. Kinase dysfunctions have been linked to numerous human diseases such as cancer. This has led to the development of kinase inhibitors which aim to target oncogenic kinase activities. The specificity of the cancer blockers depends on the range of targeted kinases. Therefore, the question arises of how cell-type-specific off-target effects impair the specificities of cancer drugs. Blockade of kinase activities has been shown to converge on the energetic organelle, the mitochondria. In this review, we highlight examples of selected major kinases which impact mitochondrial signaling. Further, we discuss pharmacological strategies to target kinase activities which are linked to cancer progression and redirecting mitochondrial function. Finally, we propose that cell-based recordings of mitochondrial bioenergetic states might predict off-target or identify specific on-target effects of kinase inhibitors.ic on-target effects of kinase inhibitors.)
Heichler 2022 MitoFit + ([[Wolf 2022 Abstract Bioblast]]: The CYRIS … [[Wolf 2022 Abstract Bioblast]]: The CYRIS® analysis platform is a multi-sensory approach to extract a large amount of information from a single cell-based assay automatically and in real-time. To demonstrate its capabilities, we performed an in-vitro hepatotoxicity assay with Acetaminophen and HepG2, with simultaneous monitoring of the key parameters oxygen consumption rate (OCR), extracellular acidification rate (ECAR), impedance and microscopic imaging. After 12 hours prior treatment measurement, different concentrations of Acetaminophen were tested over 24 hours, followed by 12 hours washout. The metabolic results showed a strong time- and dose-dependent change of OCR and ECAR through Acetaminophen. Morphologic changes monitored by impedance and microscopic imaging underpin these metabolic effects. The washout of Acetaminophen results in cellular regeneration in all parameters up to a concentration of 10 mM. The continuous measurement of OCR, ECAR, impedance and microscopic imaging enables multiparametric monitoring of cellular metabolic responses due to Acetaminophen in a single assay and provides an overall picture of its hepatotoxic effects.verall picture of its hepatotoxic effects.)
PSSA 2016 Cape Town ZA + ([http://physiolsoc.org.za/pssa-2016-conference/ PSSA conference 2016])
SSMFRP - Redox Medicine + ([http://ssmfrp.edu.rs/home SSMFRP - Redox … [http://ssmfrp.edu.rs/home SSMFRP - Redox Medicine] - 2015 Sep 25-26, Belgrade, RS'''The motto of this congress is Redox medicine, with the aim to unite research related to mitochondria and redox processes in pathophysiological conditions.''' :» [[Media: SSMFRP Preliminary scientific program.pdf| Preliminary scientific program]][Media: SSMFRP Preliminary scientific program.pdf| Preliminary scientific program]])
Laner 2013 ASMRM + ([http://www.asmrm2013.com/common_files/pro … [http://www.asmrm2013.com/common_files/program.asp Luncheon Seminar Nov 5, 12:10-12:50, ASMRM2013, Seoul, South Korea] - [http://www.oroboros.at/?O2k-workshops IOC81][[High-resolution respirometry]] (HRR) has become established world-wide for the diagnosis of mitochondrial respiratory control and OXPHOS analysis, reflected in [[O2k-Publications|>1,000 O2k-publications]] using the Oroboros Oxygraph-2k. The [[O2k-Fluorescence LED2-Module]] is a recent extension of the Oxygraph-2k for combining HRR and fluorometric measurements. Two major applications of O2k-Fluorometry are presented. # [[MiPNet18.05 Amplex-Mouse-heart|H2O2 production measured with Amplex® Ultrared in mouse heart mitochondria]] was not only a function of respiratory substrate and coupling state, but depended strongly on experimental oxygen levels below and even above air saturation of the respiration medium.# Mitochondrial membrane potential was measured with [[Safranin]] (2 µM) with high sensitivity particularly in the range of low membrane potentials. However, Safranin specifically inhibited Complex I linked respiration and the phosphorylation system, such that meaningful applications had to be restricted to Complex II linked respiration with succinate and rotenone. Inhibitory side effects must be critically evaluated for any probe of mitochondrial membrane potential. These examples illustrate the sensitivity and wide range of applicability of O2k-fluorometry and demonstrate the importance of combining measurements of hydrogen peroxide production and mitochondrial membrane potential with simultaneous monitoring of oxygen concentration and oxygen consumption.multaneous monitoring of oxygen concentration and oxygen consumption.)
Stem Cell Energetics 2014 + ([http://www.cell-symposia-stem-cell-energetics.com/ Cell Symposium Stem Cell Energetics 2014], Berkeley, CA, US.)
ISMM2014 + ([http://www.ismm2014.org/Pages/default.aspx '''World Congress on High Altitude Medicine and Physiology'''], ISMM, Bolzano, Italy; including '''[[MiPNet19.05 | 90th Oroboros O2k-Workshop]]'''.)
EUROMIT2017 Cologne DE + ([https://euromit2017.org/ EUROMIT2017] International Meeting on Mitochondrial Pathology, Cologne, DE)

Analytica China 2024 Shanghai CN + (analytica China, Shanghai, China, 2024)

Cecatto 2020 Toxicol In Vitro + (cis-5-Tetradecenoic (cis-5) and myristic ( … cis-5-Tetradecenoic (cis-5) and myristic (Myr) acids predominantly accumulate in patients affected by very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. They commonly manifest myopathy with muscular pain and rhabdomyolysis, whose underlying mechanisms are poorly known. Thus, in the present study we investigated the effects of cis-5 and Myr on mitochondrial bioenergetics and Ca2+ homeostasis in rat skeletal muscle. cis-5 and Myr decreased ADP-stimulated (state 3) and CCCP-stimulated (uncoupled) respiration, especially when mitochondria were supported by NADH-linked as compared to FADH2-linked substrates. In contrast, these fatty acids increased resting respiration (state 4). Similar effects were observed in skeletal muscle fibers therefore validating the data obtained with isolated mitochondria. Furthermore, cis-5 and Myr markedly decreased mitochondrial membrane potential and Ca2+ retention capacity that were avoided by cyclosporin A plus ADP and ruthenium red, indicating that cis-5 and Myr induce mitochondrial permeability transition (MPT). Finally, docosanoic acid did not disturb mitochondrial homeostasis, indicating selective effects for Myr and cis-5. Taken together, our findings indicate that major long-chain fatty acids accumulating in VLCAD deficiency behave as metabolic inhibitors, uncouplers of oxidative phosphorylation and MPT inducers. It is presumed that these pathomechanisms contribute to the muscular symptoms and rhabdomyolysis observed in patients affected by VLCAD deficiency.Copyright © 2019 Elsevier Ltd. All rights reserved.eficiency. Copyright © 2019 Elsevier Ltd. All rights reserved.)
EPN Autumn School Series Ebsdorfergrund DE + (he European Psychoneuroimmunology Autumn S … he European Psychoneuroimmunology Autumn School Series - the skin-brain axis and the breaking of barriers, Ebsdorfergrund, Germany, 2023 == Venue == :::: Schloss Rauischholzhausen:::: Ferdinand-von-Stumm-Straße:::: 35085 Ebsdorfergrund, Germany::::[https://www.uni-giessen.de/en/about/rhh Location]== Program ==:::: Please find the preliminary program [https://www.uni-giessen.de/de/fbz/fb10/institute_klinikum/institute/vphysbio/forschung/congresses/EPN%20Autumn%20School%20Series/Preliminary%20programs '''»here''']== Organizers == :::: The school is organized by the [https://pnieurope.eu/ European PNI Network (EPN)] and [https://www.gebin.org/ German-Endocrine-Brain-Immune-Network (GEBIN)]:::: Eva MJ Peters:::: Christoph Rummel:::: Karsten Krüger:::: Adriana del Reyl :::: Karsten Krüger :::: Adriana del Rey)
Komlodi 2021 MitoFit Q + (https://www.bioenergetics-communications.o … https://www.bioenergetics-communications.org/index.php/bec/article/view/komlodi_2021_amr''Published in'' [[Bioenergetics Communications]]: 2021-11-11::: Komlódi T, Cardoso LHD, Doerrier C, Moore AL, Rich PR, Gnaiger E (2021) Coupling and pathway control of coenzyme Q redox state and respiration in isolated mitochondria. Bioenerg Commun 2021.3. https://doi.org/10.26124/bec:2021-0003::: Version 4 ('''v4''') 2021-09-15 [http://www.mitofit.org//images/9/91/Komlodi_2021_MitoFit_Q.pdf doi:10.26124/mitofit:2021-0002.v4] ::: Version 3 (v3) 2021-09-01 [https://www.mitofit.org/images/archive/9/91/20210915113223%21Komlodi_2021_MitoFit_Q.pdf doi:10.26124/mitofit:2021-0002.v3]::: Version 2 (v2) 2021-05-06 [https://wiki.oroboros.at/images/archive/9/91/20210901145411%21Komlodi_2021_MitoFit_Q.pdf doi:10.26124/mitofit:2021-0002.v2]::: Version 1 (v1) 2021-02-18 [https://wiki.oroboros.at/images/archive/9/91/20210505231707%21Komlodi_2021_MitoFit_Q.pdf doi:10.26124/mitofit:2021-0002] - [http://www.mitofit.org/index.php/File:Komlodi_2021_MitoFit_Q.pdf#Links_to_all_versions »Link to all versions«] Redox states of the mitochondrial coenzyme Q pool, which reacts with the electron transfer system, reflect the balance between (''1'') reducing capacities of electron flow from fuel substrates converging at the Q-junction, (''2'') oxidative capacities downstream of Q to O2, and (''3'') the load on the OXPHOS system utilizing or dissipating the protonmotive force. A three-electrode sensor (Rich 1988; Moore et al 1988) was implemented into the NextGen-O2k to monitor continuously the redox state of CoQ2 added as a Q-mimetic simultaneously with O2 consumption. The Q-Module was optimized for high signal-to-noise ratio, minimum drift, and minimum oxygen diffusion. CoQ2 equilibrates in the same manner as Q at Complexes CI, CII and CIII. The CoQ2 redox state is monitored amperometrically with the working electrode, which is poised at CoQ2 redox peak potentials determined by cyclic voltammetry. The voltammogram also provides quality control of the Q-sensor and reveals chemical interferences. The CoQ2 redox state and O2 consumption were measured simultaneously in isolated mouse cardiac and brain mitochondria. CoQ2 ― and by implication mitochondrial Q ― was more oxidized when O2 flux was stimulated by coupling control: when energy demand increased from LEAK to OXPHOS and electron transfer capacities in the succinate pathway. In contrast, CoQ2 was more reduced when O2 flux was stimulated by pathway-control of electron input capacities, increasing from the NADH (N)- to succinate (S)-linked pathway which converge at the Q-junction, with CI-Q-CIII and CII-Q-CIII segments, respectively. N- and S- respiratory pathway capacities were not completely additive, compatible with partitioning of Q intermediary between the solid-state and liquid-state models of supercomplex organization. The direct proportionality of CoQ2 reduction and electron input capacities through the CI-Q-CIII and CII-Q-CIII segments suggests that CoQ2 is accurately mimicking mitochondrial Q-redox changes. and electron input capacities through the CI-Q-CIII and CII-Q-CIII segments suggests that CoQ2 is accurately mimicking mitochondrial Q-redox changes.)
Kelly 2015 Biotechnol J + (microRNA engineering of CHO cells has alre … microRNA engineering of CHO cells has already proved successful in enhancing various industrially relevant phenotypes and producing various recombinant products. A single miRNA's ability to interact with multiple mRNA targets allows their regulatory capacity to extend to processes such as cellular metabolism. Various metabolic states have previously been associated with particular CHO cell phenotypes such as glycolytic or oxidative metabolism accommodating growth and productivity, respectively. miR-23 has previously been demonstrated to play a role in glutamate metabolism resulting in enhanced oxidative phosphorylation through the TCA cycle. Re-programming cellular bioenergetics through miR-23 could tip the balance, forcing mammalian production cells to be more productive by favoring metabolic channelling into oxidative metabolism. CHO clones depleted of miR-23 using a miR-sponge decoy demonstrated an average ∼three-fold enhanced specific productivity with no impact on cell growth. Using a cell respirometer, mitochondrial activity was found to be enhanced by ∼30% at Complex I and II of the electron transport system. Additionally, label-free proteomic analysis uncovered various potential novel targets of miR-23 including LE™1 and IDH1, both implicated in oxidative metabolism and mitochondrial activity. These results demonstrate miRNA-based engineering as a route to re-programming cellular metabolism resulting in increased productivity, without affecting growth.ed productivity, without affecting growth.)
Mitochondrial Medicine 2019 Zurich CH + (mitoNET Meeting and Mitochondrial Medicine congress (Germany, Austria, Switzerland), Zurich, Switzerland, 2019)
MtFOIE GRAS Mid-term meeting Pisa IT + (mtFOIE GRAS Mid-term meeting, Pisa, Italy, 2018)
McKeehan 1982 Cell Biol Int Rep + (mtNAD-ME is crucial for the metabolism generating pyruvate from glutamine, which is the most abundant single amino acid in plasma, tissues and cell culture media. 'Glutaminolysis' is analogous to the glycolysis pathway that converts glucose to pyruvate.)
Wu 2022 Front Chem + (nFe3O4 was prepared from waste iron slag a … nFe3O4 was prepared from waste iron slag and loaded onto air stone (named magnetic air stone or MAS in the following text). The main component of air stone is carborundum. To study the magnetic effects of MAS on denitrification, a biofilm reactor was built, and its microbial community structure and electron transfer in denitrification were analyzed. The results showed that MAS improved the performance of the reactor in both carbon and nitrogen removal compared with air stone (AS) control, and the average removal efficiencies of COD, TN, and NH4 +-N increased by 17.15, 16.1, and 11.58%, respectively. High-throughput sequencing revealed that magnetism of MAS had a significant effect on the diversity and richness of microorganisms in the biofilm. The MAS also reduced the inhibition of rotenone, mipalene dihydrochloride (QDH), and sodium azide on the respiratory chain in denitrification and enhanced the accumulation of nitrite, in order to provide sufficient substrate for the following denitrification process. Therefore, the denitrification process is accelerated by the MAS. The results allowed us to deduce the acceleration sites of MAS in the denitrification electron transport chain. The existence of MAS provides a new rapid method for the denitrifying electron transport process. Even in the presence of respiratory inhibitors of denitrifying enzymes, the electron transfer acceleration provided by MAS still exists objectively. This is the mechanism through which MAS can restore the denitrification process inhibited by respiratory inhibitors to a certain extent.espiratory inhibitors to a certain extent.)
Jansen-Duerr 2016 Abstract Mito Xmas Meeting Innsbruck + (no abstract)
14th Mitochondrial Disease Conference 2024 Padova IT + (tba)
AMCTB 2016 Anal Methods + (z-Scores were devised to provide a transpa … z-Scores were devised to provide a transparent but widely-applicable scoring system for participants in proficiency tests for analytical laboratories. The essential idea is to provide an appropriate scaling of the difference between a participant’s result and the ‘assigned value’ for the concentration of the analyte. Interpretation of a z-score is straightforward but some aspects need careful attention to avoid misconception. Over time several related scores have been devised to cope with a diversified range of applications. The main types of score have recently been codified in ISO 13528 (2015).ecently been codified in ISO 13528 (2015).)
Laner 2013 Mitochondr Physiol Network MiP2013 + (» [[MiP2013 Abstracts]] » [[Laner 2013 Mitochondr Physiol Network MiP2013]])
Lehto 2022 Neurochem Res + (ß-Hydroxybutyrate (BHB) is a ketone body f … ß-Hydroxybutyrate (BHB) is a ketone body formed in high amounts during lipolysis and fasting. Ketone bodies and the ketogenic diet were suggested as neuroprotective agents in neurodegenerative disease. In the present work, we induced transient ischemia in mouse brain by unilaterally occluding the middle cerebral artery for 90 min. BHB (30 mg/kg), given immediately after reperfusion, significantly improved the neurological score determined after 24 h. In isolated mitochondria from mouse brain, oxygen consumption by the complexes I, II and IV was reduced immediately after ischemia but recovered slowly over 1 week. The single acute BHB administration after reperfusion improved complex I and II activity after 24 h while no significant effects were seen at later time points. After 24 h, plasma and brain BHB concentrations were strongly increased while mitochondrial intermediates (citrate, succinate) were unchanged in brain tissue. Our data suggest that a single administration of BHB may improve mitochondrial respiration for 1-2 days but not for later time points. Endogenous BHB formation seems to complement the effects of exogenous BHB administration.e effects of exogenous BHB administration.)
Fets 2018 Nat Chem Biol + (α-Ketoglutarate (αKG) is a key node in man … α-Ketoglutarate (αKG) is a key node in many important metabolic pathways. The αKG analog N-oxalylglycine (NOG) and its cell-permeable prodrug dimethyloxalylglycine (DMOG) are extensively used to inhibit αKG-dependent dioxygenases. However, whether NOG interference with other αKG-dependent processes contributes to its mode of action remains poorly understood. Here we show that, in aqueous solutions, DMOG is rapidly hydrolyzed, yielding methyloxalylglycine (MOG). MOG elicits cytotoxicity in a manner that depends on its transport by monocarboxylate transporter 2 (MCT2) and is associated with decreased glutamine-derived tricarboxylic acid-cycle flux, suppressed mitochondrial respiration and decreased ATP production. MCT2-facilitated entry of MOG into cells leads to sufficiently high concentrations of NOG to inhibit multiple enzymes in glutamine metabolism, including glutamate dehydrogenase. These findings reveal that MCT2 dictates the mode of action of NOG by determining its intracellular concentration and have important implications for the use of (D)MOG in studying αKG-dependent signaling and metabolism.ng αKG-dependent signaling and metabolism.)
Bir 2013 Abstract MiP2013 + (α-Synucleinopathy and mitochondrial dysfun … α-Synucleinopathy and mitochondrial dysfunction are important elements of sporadic Parkinson’s disease (PD) pathogenesis [1]. It is, however, not clear whether the accumulated α-synuclein in degenerating dopaminergic neurons in PD causes mitochondrial injury and subsequent cell death. Our earlier study has shown that α-synuclein causes functional impairment of rat brain mitochondria incubated in vitro [2].Mitochondrial membrane potential was measured using the carbocyanine dye JC1, and the phosphorylation capacity determined spectrophotometrically from inorganic phosphate utilization [2,3]. The respiratory functions of mitochondria in isolated preparations and within intact cells were analyzed by high-resolution respirometry. α-Synuclein accumulation within SHSY5Y cells was induced by lactacystin treatment and detected by immunoblotting. The transfection of SHSY5Y cells with α synuclein specific SiRNA was carried out using the lipofectamine kit (Invitrogen).Our results show that α-synuclein causes a loss of membrane potential and phosphorylation capacity with alterations in respiratory parameters in isolated rat brain mitochondria. Some of these effects were inhibited very significantly by cyclosporine (1 μM). When SHSY5Y cells were exposed to 5 μM lactacystin for 24 h, α-synuclein accumulation occured intracellularly as detected by immunoblotting experiments. Further, lactacystin treatment of SHSY5Y cells also leads to mitochondrial dysfunction and cell death concomitant with α synuclein accumulation. To confirm the involvement of α synuclein in lactacystin induced mitochondrial dysfunction, the effects of cyclosporine and the gene silencing of α-synuclein with specific SiRNA on these phenomena are being investigated.on these phenomena are being investigated.)
Sobotka 2014 Abstract IOC95 + (α-Tocopheryl succinate (TOS) is a redox-si … α-Tocopheryl succinate (TOS) is a redox-silent analogue of vitamin E with specific anti-tumorous effects. According to some studies, TOS suppresses cell growth and induces apoptosis in cancer cells [1-3]. The inhibitory effect on transformed cells is related to an increase in reactive oxygen species (ROS) production possibly via inhibition of respiratory complex II - specifically mitochondrial flavoprotein-dependent enzymes succinate dehydrogenase (SDH) and glycerol-3-phosphate dehydrogenase (mGPDH) [1-4]. On the molecular level the effect of TOS is explained by interaction of TOS with the proximal and distal CoQ-binding sites of complex II [4]. However such effect was not found in non-cancer cells [1, 3].The aim of our study was to assess the inhibitory action of TOS on complex II in rat heart and liver homogenate and mitochondria. The maximum respiratory capacity of complex II induced by addition of succinate, cytochrome c and ADP was measured using the high resolution respirometry (HRR) Oroboros 2K. We evaluated the TOS inhibitory action on complex II respiration during concentration increase. The strong inhibitory effect of TOS on complex II respiration was found at the concentration range between 150-500 μM. Our results showed that both liver and heart mitochondria were more sensitive to TOS inhibitory action in comparison to homogenate.Our study using HRR method showed a TOS inhibitory action on complex II activity. Strong inhibitory effect was detected on heart and liver mitochondria as well as on the homogenate. Lower sensitivity of liver homogenate compared to mitochondria may be the result of the presence of cytosolic esterases which split the molecule of TOS to α-tocopherol and succinate [3] or due to binding of TOS to cytosolic membrane structures.References:1. Angulo-Molina, A., et al., The Role of Alpha Tocopheryl Succinate (alpha-TOS) as a Potential Anticancer Agent. Nutr Cancer, 2013.2. Zhao, Y., J. Neuzil, and K. Wu, Vitamin E analogues as mitochondria-targeting compounds: from the bench to the bedside? Mol Nutr Food Res, 2009. 53(1): p. 129-39.3. Neuzil, J., et al., Molecular mechanism of 'mitocan'-induced apoptosis in cancer cells epitomizes the multiple roles of reactive oxygen species and Bcl-2 family proteins. FEBS Lett, 2006. 580(22): p. 5125-9.4. Rauchova, H., M. Vokurkova, and Z. Drahota, Inhibition of mitochondrial glycerol-3-phosphate dehydrogenase by alpha-tocopheryl succinate. Int J Biochem Cell Biol, 2014. 53: p. 409-13. J Biochem Cell Biol, 2014. 53: p. 409-13.)
Rauchova 2014 Int J Biochem Cell Biol + (α-Tocopheryl succinate (TOS), a redox-sile … α-Tocopheryl succinate (TOS), a redox-silent analogue of vitamin E, suppresses cell growth in a numberof clinical and experimental cancers, inhibits mitochondrial succinate dehydrogenase (SDH) and activatesreactive oxygen species (ROS) generation. The aim of this study was to test whether TOS alsoinhibits glycerol-3-phosphate dehydrogenase (mGPDH), another flavoprotein-dependent enzyme of themitochondrial respiratory chain because there are differences between electron transfer pathway fromSDH and mGPDH to coenzyme Q pool. For our experiments brown adipose tissue mitochondria withhigh expression of mGPDH were used. Our data showed that inhibition of glycerol-3-phosphate (GP)-dependent oxygen consumption by TOS was more pronounced than the succinate (SUC)-dependent one(50% inhibition was reached at 10 μmol/l TOS vs. 80 μmol/l TOS, respectively). A comparison of theinhibitory effect of TOS on GP-oxidase, GP-cytochrome c oxidoreductase and GP-dehydrogenase activitiesshowed that TOS directly interacts with the dehydrogenase. After TOS application the GP-dependentgeneration of ROS was highly depressed. It may thus be concluded that TOS-induced inhibition of mGPDHis more pronounced than TOS-induced inhibition of SDH and that the inhibitory effect of TOS for bothsubstrates is exerted at different locations of the particular dehydrogenases. Our data indicate that theinhibition of mGPDH activity could also play a role in TOS-induced growth suppression in neoplastic cells.ed growth suppression in neoplastic cells.)
Fets 2022 Commun Biol + (α-ketoglutarate (αKG) is a central metabol … α-ketoglutarate (αKG) is a central metabolic node with a broad influence on cellular physiology. The αKG analogue N-oxalylglycine (NOG) and its membrane-permeable pro-drug derivative dimethyl-oxalylglycine (DMOG) have been extensively used as tools to study prolyl hydroxylases (PHDs) and other αKG-dependent processes. In cell culture media, DMOG is rapidly converted to MOG, which enters cells through monocarboxylate transporter MCT2, leading to intracellular NOG concentrations that are sufficiently high to inhibit glutaminolysis enzymes and cause cytotoxicity. Therefore, the degree of (D)MOG instability together with MCT2 expression levels determine the intracellular targets NOG engages with and, ultimately, its effects on cell viability. Here we designed and characterised a series of MOG analogues with the aims of improving compound stability and exploring the functional requirements for interaction with MCT2, a relatively understudied member of the SLC16 family. We report MOG analogues that maintain ability to enter cells via MCT2, and identify compounds that do not inhibit glutaminolysis or cause cytotoxicity but can still inhibit PHDs. We use these analogues to show that, under our experimental conditions, glutaminolysis-induced activation of mTORC1 can be uncoupled from PHD activity. Therefore, these new compounds can help deconvolute cellular effects that result from the polypharmacological action of NOG.rom the polypharmacological action of NOG.)
Horvath 2022 Antioxidants (Basel) + (α-ketoglutarate dehydrogenase complex (KGD … α-ketoglutarate dehydrogenase complex (KGDHc), or 2-oxoglutarate dehydrogenase complex (OGDHc) is a rate-limiting enzyme in the tricarboxylic acid cycle, that has been identified in neurodegenerative diseases such as in Alzheimer's disease. The aim of the present study was to establish the role of the KGDHc and its subunits in the bioenergetics and reactive oxygen species (ROS) homeostasis of brain mitochondria. To study the bioenergetic profile of KGDHc, genetically modified mouse strains were used having a heterozygous knock out (KO) either in the dihydrolipoyl succinyltransferase (DLST+/-) or in the dihydrolipoyl dehydrogenase (DLD+/-) subunit. Mitochondrial oxygen consumption, hydrogen peroxide (H2O2) production, and expression of antioxidant enzymes were measured in isolated mouse brain mitochondria. Here, we demonstrate that the ADP-stimulated respiration of mitochondria was partially arrested in the transgenic animals when utilizing α-ketoglutarate (α-KG or 2-OG) as a fuel substrate. Succinate and α-glycerophosphate (α-GP), however, did not show this effect. The H2O2 production in mitochondria energized with α-KG was decreased after inhibiting the adenine nucleotide translocase and Complex I (CI) in the transgenic strains compared to the controls. Similarly, the reverse electron transfer (RET)-evoked H2O2 formation supported by succinate or α-GP were inhibited in mitochondria isolated from the transgenic animals. The decrease of RET-evoked ROS production by DLST+/- or DLD+/- KO-s puts the emphasis of the KGDHc in the pathomechanism of ischemia-reperfusion evoked oxidative stress. Supporting this notion, expression of the antioxidant enzyme glutathione peroxidase was also decreased in the KGDHc transgenic animals suggesting the attenuation of ROS-producing characteristics of KGDHc. These findings confirm the contribution of the KGDHc to the mitochondrial ROS production and in the pathomechanism of ischemia-reperfusion injury.stics of KGDHc. These findings confirm the contribution of the KGDHc to the mitochondrial ROS production and in the pathomechanism of ischemia-reperfusion injury.)
Risiglione 2022 Life (Basel) + (α-synuclein (αSyn) is a small neuronal pro … α-synuclein (αSyn) is a small neuronal protein whose accumulation correlates with Parkinson's disease. αSyn A53T mutant impairs mitochondrial functions by affecting substrate import within the organelle, activity of complex I and the maximal respiratory capacity. However, the precise mechanism initiating the bioenergetic dysfunction is not clearly understood yet. By overexpressing αSyn A53T in SH-SY5Y cells, we investigated the specific changes in the mitochondrial respiratory profile using High-Resolution Respirometry. We found that αSyn A53T increases dissipative fluxes across the intermembrane mitochondrial space: this does not compromise the oxygen flows devoted to ATP production while it reduces the bioenergetic excess capacity of mitochondria, providing a possible explanation of the increased cell susceptibility observed in the presence of further stress stimuli.in the presence of further stress stimuli.)
Martinez 2018 Arch Biochem Biophys + (α-synuclein is involved in both familial a … α-synuclein is involved in both familial and sporadic Parkinson's disease. Although its interaction with mitochondria has been well documented, several aspects remain unknown or under debate such as the specific sub-mitochondrial localization or the dynamics of the interaction. It has been suggested that α-synuclein could only interact with ER-associated mitochondria. The vast use of model systems and experimental conditions makes it difficult to compare results and extract definitive conclusions. Here we tackle this by analyzing, in a simplified system, the interaction between purified α-synuclein and isolated rat brain mitochondria. This work shows that wild type α-synuclein interacts with isolated mitochondria and translocates into the mitochondrial matrix. This interaction and the irreversibility of α-synuclein translocation depend on incubation time and α-synuclein concentration. FRET experiments show that α-synuclein localizes close to components of the TOM complex suggesting a passive transport of α-synuclein through the outer membrane. In addition, α-synuclein binding alters mitochondrial function at the level of Complex I leading to a decrease in ATP synthesis and an increase of ROS production.nthesis and an increase of ROS production.)
Gregg 2019 J Biol Chem + (β-cell mitochondria play a central role in … β-cell mitochondria play a central role in coupling glucose metabolism with insulin secretion. Here, we identified a metabolic function of cyclin-dependent kinase 1 (CDK1)/cyclin B1 - the activation of mitochondrial respiratory Complex I - that is active in quiescent adult β-cells and hyperactive in β-cells from obese (''ob/ob'') mice. In wild-type islets, respirometry revealed that 65 % of Complex I flux and 49 % of state 3 respiration is sensitive to CDK1 inhibition. Islets from ''ob/ob'' mice expressed more cyclin B1 and exhibited a higher sensitivity to CDK1 blockade, which reduced Complex I flux by 76 % and state 3 respiration by 79 %. The ensuing reduction in mitochondrial NADH utilization, measured with 2-photon NAD(P)H fluorescence lifetime imaging (FLIM), was matched in the cytosol by a lag in citrate cycling, as shown with a FRET reporter targeted to β-cells. Moreover, time-resolved measurements revealed that in ''ob/ob'' islets, where Complex I flux dominates respiration, CDK1 inhibition is sufficient to restrict the duty cycle of ATP/ADP and calcium oscillations, the parameter that dynamically encodes β-cell glucose sensing. Direct Complex I inhibition with rotenone mimicked the restrictive effects of CDK1 inhibition on mitochondrial respiration, NADH turnover, ATP/ADP, and calcium influx. These findings identify Complex I as a critical mediator of obesity-associated metabolic remodeling in β-cells, and implicate CDK1 as a regulator of Complex I that enhances β-cell glucose sensing.Published under license by The American Society for Biochemistry and Molecular Biology, Inc.Biochemistry and Molecular Biology, Inc.)
D'Onofrio 2020 Sci Rep + (δ-Valerobetaine (δVB) is a constitutive mi … δ-Valerobetaine (δVB) is a constitutive milk metabolite with antioxidant and anti-inflammatory activities. Here, we tested the antineoplastic properties of milk δVB on human colorectal cancer cells. CCD 841 CoN (non-tumorigenic), HT-29 (p53 mutant adenocarcinoma) and LoVo (APC/RAS mutant adenocarcinoma) cells were exposed to 3 kDa milk extract, δVB (2 mM) or milk+δVB up to 72 h. Results showed a time- and dose-dependent capability of δVB to inhibit cancer cell viability, with higher potency in LoVo cells. Treatment with milk+δVB arrested cell cycle in G2/M and SubG1 phases by upregulating p21, cyclin A, cyclin B1 and p53 protein expressions. Noteworthy, δVB also increased necrosis (P < 0.01) and when used in combination with milk it improved its activity on live cell reduction (P < 0.05) and necrosis (P < 0.05). δVB-enriched milk activated caspase 3, caspase 9, Bax/Bcl-2 apoptotic pathway and reactive oxygen species (ROS) production, whereas no effects on ROS generation were observed in CCD 841 CoN cells. The altered redox homeostasis induced by milk+δVB was accompanied by upregulation of sirtuin 6 (SIRT6). SIRT6 silencing by small interfering RNA blocked autophagy and apoptosis activated by milk+δVB, unveiling the role of this sirtuin in the ROS-mediated apoptotic LoVo cell death.tuin in the ROS-mediated apoptotic LoVo cell death.)
Gnaiger 2018 EBEC2018 + (‘.. ''the sum of the '''electrical pressur … ‘.. ''the sum of the '''electrical pressure difference''' and the '''osmotic pressure difference''' (i.e. the electrochemical potential difference) of protons''’ [1] links to non-ohmic flux-force relationships between proton leak and protonmotive force ''pmF''. This is experimentally established, has direct consequences on mitochondrial physiology, but is theoretically little understood [2,3]. Here I distinguish pressure from potential differences (diffusion: Δ''μ''H+ or Δd''F''H+; electric: Δ''Ψ'' or Δel''F''p+), to explain non-ohmic flux-'''[[force]]''' relationships on the basis of four thermodynamic theorems. (''1'') Einstein’s diffusion equation [4] explains the [[concentration]] gradient (d'''''c'''''/d'''''z''''') in Fick’s law as the product of chemical potential gradient (the vector force and resistance determine the velocity '''''v''''' of a particle) and local concentration '''''c'''''. This yields the chemical [[pressure]] gradient (van’t Hoff): d'''d''''''''Π'''''/d'''''z''''' = ''RT''∙d'''''c'''''/'''d''z'''''. [[Flux]] [5] is the product of '''''v''''' and '''''c'''''; '''''c''''' varies with force. Therefore, flux-force relationships are non-linear. (''2'') The ''pmF'' is not a vector force; the gradient is replaced by a pressure difference, and local concentration by a distribution function or free activity ''α''. Flux is a function of ''α'' and force, ''J''d = -''u''d∙''α''∙Δd''FX'' = -''u''d∙Δd''ΠX'' [6]. (''3'') At Δel''F''p+ = -Δd''F''H+, the diffusion pressure of protons, Δd''Π''H+ = ''RT''∙Δ''c''H+ [Pa=J∙m-3] is balanced by electric pressure, maintained by counterions of H+. Diffusional and electric pressures are isomorphic, additive, and yield protonmotive pressure ''pmp''. (''4'') The dependence of [[proton leak]] on ''pmF'' varies with Δel''F''p+ versus Δd''F''H+, in agreement with experimental evidence. The flux-force relationship is concave at high mitochondrial volume fractions, but near-exponential at small mt-matrix volume ratios. Linear flux-''pmp'' relationships imply a near-exponential dependence of the proton leak on the ''pmF'' ([7]; added 2022-07-04).t;sub>p+ versus Δd''F''H+, in agreement with experimental evidence. The flux-force relationship is concave at high mitochondrial volume fractions, but near-exponential at small mt-matrix volume ratios. Linear flux-''pmp'' relationships imply a near-exponential dependence of the proton leak on the ''pmF'' ([7]; added 2022-07-04).)
Gnaiger 2023 MiP2023 + (‘Obesity is a complex condition, one with … ‘Obesity is a complex condition, one with serious social and psychological dimensions, that affects virtually all age and socioeconomic groups and threatens to overwhelm both developed and developing countries’ ― the WHO perspective on ‘globesity’ (https://www.who.int/activities/controlling-the-global-obesity-epidemic). Obesity defined as [[BMI]]≥30 (WHO) is biased, overestimating obesity thresholds in taller persons (men) but underestimating it in smaller groups (women) ― a gender data gap. Here obesity is defined as accumulation of excess fat-tissue mass, ''M''FE=''M''F-''M''F°. ''M''F° is the fat mass per individual in the [[healthy reference population]] at any height and body mass ''M''° without overweight. Body fat excess, BFE=''M''FE/''M''°, is related to body mass excess, [[BME]]=''M''E/''M''°, where ''M''E=''M''-''M''°. A balanced BME is BME° = 0.0 with a band width of -0.1 towards underweight and +0.2 towards pre-obesity (overweight). The BME is linearly related to the body fat excess in women and men with statistical implications on mitochondrial functional fitness.[[File:MitObesity-and-comorbidities.jpg|500px|right|link=Category:BME_and_mitObesity|mitObesity]]Aerobic spiroergometric capacity per body mass ''V''O2max/''M'' and mitochondrial respiratory capacity per muscle mass [1] decline as a function of BME. Compromised mitochondrial fitness across metabolically active organs provides a functional connection between obesity and comorbidities bound to redox imbalance, inflammation, oxidative stress, and insulin resistance: diabetes, cardiovascular and neurodegenerative diseases, various types of cancer (Figure 1). mitObesity is the leading cause of deaths and early aging, prevented by improved quality of life in active lifestyles with exercise and caloric balance. Obesity has reached the general news, without connection to mitochondria. How do we get from globesity to mitObesity to forge scientific results into knowledge impacting society, health system stakeholders, and politics? ow do we get from globesity to mitObesity to forge scientific results into knowledge impacting society, health system stakeholders, and politics? )