Defects in assembly of cytochrome oxidase: roles in mitochondrial disease

Abstract

Defects in cytochrome oxidase (COX) are a major cause of mitochondrial disease in humans and a majority of these inherited COX deficiencies stem from a failure to complete assembly of the enzyme. Studies in the yeast, Saccharomyces cerevisiae, have identified more than 30 proteins (so-called “assembly factors”) that are required for expression and assembly of a functional cytochrome oxidase and more than a dozen of these have homologs in higher eukaryotes, including Homo sapiens. This review focuses on proteins that function exclusively in the COX assembly pathway and describes our current understanding of the structure and function of several of the COX assembly factors, particularly as they relate to a variety of different inherited COX deficiencies. Studies in yeast have provided an excellent model for delineating the COX assembly pathway and should continue to inform our understanding of the molecular defects that give rise to human COX deficiencies.