A CMC1-knockout reveals translation-independent control of human mitochondrial complex IV biogenesis.

ABSTRACT: Defects in mitochondrial respiratory chain complex IV (CIV) frequently cause encephalocardiomyopathies. Human CIV assembly involves 14 subunits of dual genetic origin and multiple nucleus-encoded ancillary factors. Biogenesis of the mitochondrion-encoded copper/heme-containing COX1 subunit initiates the CIV assembly process. Here, we show that the intermembrane space twin CX₉C protein CMC1 forms an early CIV assembly intermediate with COX1 and two assembly factors, the cardiomyopathy proteins COA3 and COX14. A TALEN-mediated CMC1 knockout HEK293T cell line displayed normal COX1 synthesis but decreased CIV activity owing to the instability of newly synthetized COX1. We demonstrate that CMC1 stabilizes a COX1-COA3-COX14 complex before the incorporation of COX4 and COX5a sub

SUBMITTER: Bourens M 

PROVIDER: S-EPMC5331208 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature