Saccharomyces cerevisiae Dmo2p is required for the stability and maturation of newly translated Cox2p

Based on available platforms detailing the Saccharomyces cerevisiae mitochondrial proteome and other high‐throughput studies, we identified the yeast gene DMO2 as having a profile of genetic and physical interactions that indicate a putative role in mitochondrial respiration. Dmo2p is a homologue to human distal membrane‐arm assembly complex protein 1 (DMAC1); both proteins have two conserved cysteines in a Cx 2 C motif. Here, we localised Dmo2p in the mitochondrial inner membrane with the conserved cysteines facing the intermembrane space. The respiratory deficiency of dmo2 mutants at 37°C led to a reduction in cytochrome c oxidase (COX) activity (COX) and in the formation of cytochrome bc 1 complex–COX supercomplexes; dmo2 also has a rapid turnover of Cox2p, the second subunit of the COX complex that harbours the binuclear Cu A centre. Moreover, Dmo2p co‐immunoprecipitates with Cox2p and components required for maturation of the Cu A centre, such as Sco1p and Sco2p. Finally, DMO2 overexpression can suppress cox23 respiratory deficiency, a mutant that has impaired mitochondrial copper homeostasis. Mass spectrometry data unveiled the interaction of Dmo2p with different large molecular complexes, including bc 1 –COX supercomplexes, the TIM23 machinery and the ADP/ATP nucleotide translocator. Overall, our data suggest that Dmo2p is required for Cox2p maturation, potentially by aiding proteins involved in copper transport and incorporation into Cox2p.