The AMIGa complex is at the crossroads of cytochrome c oxidase and ATP synthase biogenesis

Abstract Cytochrome c oxidase (CIV) and ATP synthase are part of the oxidative phosphorylation machinery. Their modular, highly regulated assembly requires specific factors and is coordinated through a common intermediate, the Atco complex, composed of the Atp9 ring and Cox6. By high-throughput analysis, it was previously detected that Aim11 interacts with some CIV and ATP synthase subunits, but its relevance was unknown. In this work, we characterize the role of Aim11 in CIV and ATP synthase biogenesis. We find that the null mutant exhibits reduced respiratory growth and diminished CIV activity. Mitochondrial complexome profiling of the Δaim11 mutant shows an accumulation of intermediates of the CIV and ATP synthase assembly modules. Aim11 forms a complex with three other proteins: Mtc3, Gep7, and Iai11, which we coin as AMIGa (Aim11-Mtc3-Iai11-Gep7 assembly complex). Aim11 interacts with the newly synthesized Atp9 ring, possibly mediated by the Atco complex. In addition, we identify the human protein TMEM242 as an Aim11 orthologue.