HIGD2A is required for assembly of the COX3 module of human mitochondrial complex IV

Abstract

Abstract Assembly factors play a critical role in the biogenesis of the mitochondrial respiratory chain, which includes complexes I-IV. Complexes I, III and IV are found in a high molecular weight structure known as the respiratory chain supercomplex or respirasome. A number of proteins are frequently suggested to be required for supercomplex assembly, including the homolog of hypoxia inducible gene 1 domain family member HIGD2A which has been shown to stabilize the respirasome in yeast. We show that loss of HIGD2A in human cells results in impaired complex IV activity and accumulation of complex IV assembly intermediates. Using a novel pulse-proteomics approach we show HIGD2A functions in t..