COA6 Facilitates cytochrome c oxidase biogenesis as thiol-reductase for copper metallochaperones in mitochondria
Abstract: The mitochondrial cytochrome c oxidase, the terminal enzyme of the respiratory chain, contains heme and copper centers for electron transfer. The conserved COX2 subunit contains the CuA site, a binuclear copper center. The copper chaperones SCO1, SCO2, and COA6, are required for CuA center formation. Loss of function of these chaperones and the concomitant cytochrome c oxidase deficiency cause severe human disorders. Here we analyzed the molecular function of COA6 and the consequences of COA6 deficiency for mitochondria. Our analyses show that loss of COA6 causes combined complex I and complex IV deficiency and impacts membrane potential-driven protein transport across the inner membrane. We demonstrate that COA6 acts as a thiol-reductase to reduce disulfide bridges of critical cysteine residues in SCO1 and SCO2. Cysteines within the CX3CXNH domain of SCO2 mediate its interaction with COA6 but are dispensable for SCO2eSCO1 interaction. Our analyses define COA6 as thiol-reductase, which is essential for CuA biogenesis
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Journal of molecular biology. - 432, 7 (2020) , 2067-2079, ISSN: 1089-8638
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2020
- Urheber
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Pacheu-Grau, David
Wasilewski, Michal
Oeljeklaus, Silke
Gibhardt, Christine Silvia
Aich, Abhishek
Chudenkova, Margarita
Dennerlein, Sven
Deckers, Markus
Bogeski, Ivan
Warscheid, Bettina
Chacinska, Agnieszka
Rehling, Peter
- DOI
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10.1016/j.jmb.2020.01.036
- URN
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urn:nbn:de:bsz:25-freidok-1726882
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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25.03.2025, 13:41 MEZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Pacheu-Grau, David
- Wasilewski, Michal
- Oeljeklaus, Silke
- Gibhardt, Christine Silvia
- Aich, Abhishek
- Chudenkova, Margarita
- Dennerlein, Sven
- Deckers, Markus
- Bogeski, Ivan
- Warscheid, Bettina
- Chacinska, Agnieszka
- Rehling, Peter
- Universität
Entstanden
- 2020
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