Rcf1 and Rcf2, members of the hypoxia-induced gene 1 protein family, are critical components of the mitochondrial cytochrome bc1-cytochrome c oxidase supercomplex.
We report that Rcf1 (formerly Aim31), a member of the conserved hypoxia-induced gene 1 (Hig1) protein family, represents a novel component of the yeast cytochrome bc(1)-cytochrome c oxidase (COX) supercomplex. Rcf1 (respiratory supercomplex factor 1) partitions with the COX complex, and evidence that it may act as a bridge to the cytochrome bc(1) complex is presented. Rcf1 interacts with the Cox3 subunit and can do so prior to their assembly into the COX complex. A close proximity of Rcf1 and members of the ADP/ATP carrier (AAC) family was also established. Rcf1 displays overlapping function with another Hig1-related protein, Rcf2 (formerly Aim38), and their joint presence is required for optimal COX enzyme activity and the correct assembly of the cytochrome bc(1)-COX supercomplex. Rcf1 and Rcf2 can independently associate with the cytochrome bc(1)-COX supercomplex, indicating that at least two forms of this supercomplex exist within mitochondria. We provide evidence that the association with the cytochrome bc(1)-COX supercomplex and regulation of the COX complex are a conserved feature of Hig1 family members. Based on our findings, we propose a model where the Hig1 proteins regulate the COX enzyme activity through Cox3 and associated Cox12 protein, in a manner that may be influenced by the neighboring AAC proteins.
Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin, USA.
Vera
V
Strogolova
Andrew
A
Furness
Micaela
M
Robb-McGrath
Joshua
J
Garlich
Rosemary A
RA
Stuart
D014450:Electron Transport Complex III / Q000235:genetics / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology*; D008954:Models, Biological; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
D051793:Hypoxia-Inducible Factor 1; C573148:Rcf1 protein, S cerevisiae; C573149:Rcf2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D003576:Electron Transport Complex IV; D014450:Electron Transport Complex III