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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.)