Modulation of the respiratory supercomplexes in yeast: Enhanced formation of cytochrome oxidase increases the stability and abundance of respiratory supercomplexes.

Yeast deficient in the Rieske iron-sulfur subunit (Rip1) of ubiquinol-cytochrome c reductase (bc1) accumulate a late core assembly intermediate, which weakly associates with cytochrome oxidase (CcO) in a respiratory supercomplex. Expression of the N-terminal half of Rip1 which lacks the C-terminal FeS-containing globular domain (designated N-Rip1) results in a marked stabilization of trimeric and tetrameric bc1:CcO supercomplexes. Another bc1 mutant (qcr9Δ) stalled at the same assembly intermediate is likewise converted to stable supercomplex species by the expression of N-Rip1, but not by expression of intact Rip1. The N-Rip1 induced stabilization of bc1:CcO supercomplexes is independent of the Bcs1 translocase that mediates Rip1 translocation during bc1 biogenesis. N-Rip1 induces the stabilization of bc1:CcO supercomplexes through an enhanced formation of CcO. The association of N-Rip1 with the late core bc1 assembly intermediate appears to confer stabilization of a CcO assembly intermediate. This induced stabilization of CcO is dependent on the Rcf1 supercomplex stabilization factor and only partially dependent on the presence of cardiolipin. N-Rip1 exerts a related induction of CcO stabilization in WT yeast, resulting in enhanced respiration. Additionally, the impact of CcO stabilization on supercomplexes was observed by means other than expression of N-Rip1 (via over-expression of CcO subunits Cox4 and Cox5a), demonstrating this is a general phenomenon. This study is the first evidence showing that supercomplexes can be stabilized by the stimulated formation of CcO.