Abstract
The mitochondrial respiratory chain is assembled into supercomplexes. Previously, two respiratory supercomplex-associated proteins, Rcf1 and Rcf2, were identified in Saccharomyces cerevisiae, which were initially suggested to mediate supercomplex formation. Recent evidence suggests that these factors instead are involved in cytochrome c oxidase biogenesis. We demonstrate here that Rcf1 mediates proper function of cytochrome c oxidase, while binding of Rcf2 results in a decrease of cytochrome c oxidase activity. Chemical crosslink experiments demonstrate that the conserved Hig-domain as well as the fungi specific C-terminus of Rcf1 are involved in molecular interactions with the cytochrome c oxidase subunit Cox3. We propose that Rcf1 modulates cytochrome c oxidase activity by direct binding to the oxidase to trigger changes in subunit Cox1, which harbors the catalytic site. Additionally, Rcf1 interaction with cytochrome c oxidase in the supercomplexes increases under respiratory conditions. These observations indicate that Rcf1 could enable the tuning of the respiratory chain depending on metabolic needs or repair damages at the catalytic site.
Highlights
Mitochondria exert a plethora of metabolic functions including the TCA cycle, β-oxidation of fatty acids, heme synthesis, calcium storage and oxidative phosphorylation (OXPHOS) (Spinelli and Haigis, 2018)
ATP is the product of the OXPHOS system, a system of complexes residing in the inner mitochondrial membrane consisting of the respiratory chain complexes and the ATP synthase
We investigated the effect of the loss of Rcf1 and Rcf2 on respiratory ability under normal and under stress conditions using growth assays (Figure 1A)
Summary
Mitochondria exert a plethora of metabolic functions including the TCA cycle, β-oxidation of fatty acids, heme synthesis, calcium storage and oxidative phosphorylation (OXPHOS) (Spinelli and Haigis, 2018). ATP is the product of the OXPHOS system, a system of complexes residing in the inner mitochondrial membrane consisting of the respiratory chain complexes and the ATP synthase. Electrons are transferred from electron donors like NADH and FADH2 through the different complexes of the respiratory chain, which maintain a proton gradient by translocating protons across the inner mitochondrial membrane. In the yeast Saccharomyces cerevisiae the respiratory chain consists of complexes II, III, and IV. Complex III (bc complex) and Complex IV (cytochrome c oxidase) assemble to respiratory supercomplexes (III2IV and III2IV2), structures which persist in mild detergent conditions (Cruciat et al, 2000; Schägger, 2000). The function of respiratory supercomplexes is debated with proposals
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