T1121G Point Mutation in the Mitochondrial Gene Suppresses a Null Mutation in Required for the Assembly of Yeast Mitochondrial ATP Synthase.

Nuclear-encoded Atp23 was previously shown to have dual functions, including processing the yeast Atp6 precursor and assisting the assembly of yeast mitochondrial ATP synthase. However, it remains unknown whether there are genes functionally complementary to to rescue null mutant. In the present paper, we screen and characterize three revertants of null mutant and reveal a T1121G point mutation in the mitochondrial gene coding sequence, which leads to Val374Gly mutation in Cox1, the suppressor in the revertants. This was verified further by the partial restoration of mitochondrial ATP synthase assembly in null mutant transformed with exogenous hybrid   mutant plasmid. The predicted tertiary structure of the Cox1 p.Val374Gly mutation showed no obvious difference from wild-type Cox1. By further chase labeling with isotope [S]-methionine, we found that the stability of Atp6 of ATP synthase increased in the revertants compared with the null mutant. Taking all the data together, we revealed that the T1121G point mutation of mitochondrial gene could partially restore the unassembly of mitochondrial ATP synthase in null mutant by increasing the stability of Atp6. Therefore, this study uncovers a gene that is partially functionally complementary to to rescue deficiency, broadening our understanding of the relationship between yeast the cytochrome c oxidase complex and mitochondrial ATP synthase complex.