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 Cu_A site, a binuclear copper center. The copper chaperones SCO1, SCO2, and COA6, are required for Cu_A 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 o

SUBMITTER: Pacheu-Grau D 

PROVIDER: S-EPMC7254062 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature