Dennerlein 2014 Abstract IOC96: Difference between revisions

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Dennerlein S (2014) Insights into COX-assembly: An important but not the only OXPHOS complex. Mitochondr Physiol Network 19.11.

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Dennerlein S, Oeljeklaus S, Warscheid B, Rehling P (2014)

Event: IOC96

Within the last decades the development of a broad range of diagnostic methodologies led to the identification of an increasing number of human mitochondrial disease genes. Many patients present defects in the mitochondrial oxidative phosphorylation system (OXPHOS), the main energy source of the cell. The OXPHOS system is composed of the ATP producing ATP synthase (complex V), and of four multisubunit enzyme complexes, the mitochondrial respiratory chain (MRC) or complexes I-IV. In addition to the 82 structural components, an increasing number of associated factors, required for complex assembly, have been described. In contrast to the nuclear-encoded structural components, mutations in several COX assembly factors have been reported and were shown to be associated with various disorders. However, beside the growing number of identified MRC assembly factors, the understanding of the molecular mechanisms of complex IV assembly and maturation is far from complete.

We have recently identified a novel player, MITRAC12, which was shown to be in association with SURF1, a COX assembly factor, mutated in Leigh syndrome. This finding led to the identification of the MITRAC complex, a COX assembly intermediate. We have shown that MITRAC components feed back to COX1 translation and further facilitate the integration of newly imported nuclear encoded COX-subunits in the maturing enzyme via TIM21. However, the data support also an involvement of TIM21 in the maturation of all other OXPHOS complexes. Hence it is essential to get quantitative data of the activity and functionality of these complexes.

Details: Bednarczyk P, Wieckowski MR, Broszkiewicz M, Skowronek K, Siemen D, Szewczyk A. Putative Structural and Functional Coupling of the Mitochondrial BKCa Channel to the Respiratory Chain. PLoS One. 2013 Jun 27;8(6):e68125.

Labels: MiParea: Respiration, Patients

Stress:Mitochondrial Disease; Degenerative Disease and Defect"Mitochondrial Disease; Degenerative Disease and Defect" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. Organism: Human

Coupling state: OXPHOS

MITRAC12

Affiliation

Department of Biophysics, Warsaw University of Life Sciences - SGGW, Warsaw, Poland

Department of Neurology, Otto-von-Guericke-University, Magdeburg, Germany

Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology, Warsaw, Poland

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 {{Abstract
-|title=Bednarczyk P (2014) Coupling of the mitochondrial BKCa channel to the respiratory chain. Mitochondr Physiol Network 19.11.
+|title=Dennerlein S (2014) Insights into COX-assembly: An important but not the only OXPHOS complex. Mitochondr Physiol Network 19.11.
-|authors=Bednarczyk P, Siemen D, Szewczyk A
+|authors=Dennerlein S, Oeljeklaus S, Warscheid B, Rehling P
 |year=2014
 |event=IOC96
-|abstract=Potassium channels as present in the plasma membrane of various cells have also been found in the inner mitochondrial membrane. Potassium channels have been proposed to regulate the mitochondrial membrane potential, respiration, matrix volume and Ca2+ ion homeostasis. It has been suggested that mitochondrial potassium channels participate in ischemic preconditioning and neurodegenerative disorders.
+|abstract=Within the last decades the development of a broad range of diagnostic methodologies led to the identification of an increasing number of human mitochondrial disease genes. Many patients present defects in the mitochondrial oxidative phosphorylation system (OXPHOS), the main energy source of the cell. The OXPHOS system is composed of the ATP producing ATP synthase (complex V), and of four multisubunit enzyme complexes, the mitochondrial respiratory chain (MRC) or complexes I-IV. In addition to the 82 structural components, an increasing number of associated factors, required for complex assembly, have been described. In contrast to the nuclear-encoded structural components, mutations in several COX assembly factors have been reported and were shown to be associated with various disorders. However, beside the growing number of identified MRC assembly factors, the understanding of the molecular mechanisms of complex IV assembly and maturation is far from complete.
-In our study single channel activity of a large conductance Ca2+-regulated potassium channel was measured by patch-clamp of mitoplasts isolated from an astrocytoma cell line. A potassium selective current was recorded with a mean conductance of 290 pS in symmetrical 150 mM KCl solution. The channel was activated by Ca2+ at micromolar concentrations and inhibited irreversibly by iberiotoxin, an selective inhibitor of the BKCa channel. Additionally, we showed that substrates of the respiratory chain like NADH, succinate, and glutamate/malate, decrease the activity of the channel at positive voltages. The effect was abolished by rotenone, antimycin and cyanide, being inhibitors of respiratory chain.
-Our findings indicate that mitochondrial large conductance Ca2+-regulated potassium channels with properties similar to the surface membrane BKCa channel are present in human astrocytoma mitochondria and can be stimulated by redox status of the respiratory chain.
+We have recently identified a novel player, MITRAC12, which was shown to be in association with SURF1, a COX assembly factor, mutated in Leigh syndrome. This finding led to the identification of the MITRAC complex, a COX assembly intermediate. We have shown that MITRAC components feed back to COX1 translation and further facilitate the integration of newly imported nuclear encoded COX-subunits in the maturing enzyme via TIM21. However, the data support also an involvement of TIM21 in the maturation of all other OXPHOS complexes. Hence it is essential to get quantitative data of the activity and functionality of these complexes.
 Details: Bednarczyk P, Wieckowski MR, Broszkiewicz M, Skowronek K, Siemen D, Szewczyk A. Putative Structural and Functional Coupling of the Mitochondrial BKCa Channel to the Respiratory Chain. PLoS One. 2013 Jun 27;8(6):e68125.
-|keywords=Calcium-regulated potassium channel, astroycytoma, patch-clamp, mitoplast, channel activity, redox status[[File:Abstract Bednarczyk_P_Graphical.jpg|center|600px]]<div class="center" >Schematic of the proposed model and the applied substrates/inhibitors of the respiratory chain.</div> <br>
-|mipnetlab=PL Warsaw Szewczyk A, DE Magdeburg Klinik Neurologie, DE Magdeburg Siemen D
 }}
 {{Labeling
-|area=mt-Membrane
+|area=Respiration, Patients
 |organism=Human
-|tissues=Nervous system
+|injuries=Mitochondrial Disease; Degenerative Disease and Defect
-|model cell lines=Other cell lines
+|couplingstates=OXPHOS
-|preparations=SMP
+|additional=MITRAC12
-|enzymes=Inner mtMembrane Transporter
 }}
 ==Affiliation==
 Department of Biophysics, Warsaw University of Life Sciences - SGGW, Warsaw, Poland