Dmo2p is required for Cox2p stability and plays a role in mitochondrial redox balance

Abstract

AbstractAlthoughSaccharomyces cerevisiaemulti-omic studies have unveiled the function of many proteins, several with elusive functions remain to be fully understood. Based on available platforms of mitochondrial proteome and expression studies, we selected the yeast ORFYDL157cfor further characterization. In the meantime, the same ORF was identified by other groups using a machine learning approach as required for mitochondrial translation and it was renamed asDMO2. Dmo2p is a homolog to human DMAC1; it contains conserved cysteines in a Cx2C motif and was previously detected in the peroxisome and in the mitochondrial proteome. Our work discloses Dmo2p as a new factor required for the stabilization of a newly translated mitochondrial product Cox2p, the subunit two of the cytochromecoxidase complex. Three pieces of evidence have led us to this conclusion: first, elevated instability of newly translated Cox2p in thedmo2null mutant; second, Dmo2p pulled down components of Cox2p maturation and metalation processes such as Sco1p, Sco2p, and Cox2p itself; and third, expression ofDMO2in multicopy plasmids led to phenotypic suppression of thecox23mutant that has impaired copper traffic to COX metalation. Moreover, we also observed several phenotypes indmo2mutants that indicate a general function of Dmo2p in cellular stress response; the null mutant did not grow on oleate medium, it is more sensitive to heat and oxidative stress, while its overexpression confers resistance to the tested oxidants.