title: The yeast Aac2 protein exists in physical association with the cytochrome bc1-COX supercomplex and the TIM23 machinery.
abstract: The ADP/ATP carrier (AAC) proteins play a central role in cellular metabolism as they facilitate the exchange of ADP and ATP across the mitochondrial inner membrane. We present evidence here that in yeast (Saccharomyces cerevisiae) mitochondria the abundant Aac2 isoform exists in physical association with the cytochrome c reductase (cytochrome bc(1))-cytochrome c oxidase (COX) supercomplex and its associated TIM23 machinery. Using a His-tagged Aac2 derivative and affinity purification studies, we also demonstrate here that the Aac2 isoform can be affinity-purified with other AAC proteins. Copurification of the Aac2 protein with the TIM23 machinery can occur independently of its association with the fully assembled cytochrome bc(1)-COX supercomplex. In the absence of the Aac2 protein, the assembly of the cytochrome bc(1)-COX supercomplex is perturbed, whereby a decrease in the III(2)-IV(2) assembly state relative to the III(2)-IV form is observed. We propose that the association of the Aac2 protein with the cytochrome bc(1)-COX supercomplex is important for the function of the OXPHOS complexes and for the assembly of the COX complex. The physiological implications of the association of AAC with the cytochrome bc(1)-COX-TIM23 supercomplex are also discussed.
authors.affiliation: Department of Biological Sciences, Marquette University, Milwaukee, WI 53233, USA.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Dienhart
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Stuart
mesh_terms: D017209:Apoptosis; D014450:Electron Transport Complex III / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism*; D008564:Membrane Potentials; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism / Q000502:physiology*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D010100:Oxygen / Q000737:chemistry; D010641:Phenotype; D010766:Phosphorylation; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology*
chemical_list: D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C112225:PET9 protein, S cerevisiae; D020033:Protein Isoforms; D029701:Saccharomyces cerevisiae Proteins; C083081:TIM23 protein, S cerevisiae; D000226:Mitochondrial ADP, ATP Translocases; D003576:Electron Transport Complex IV; D014450:Electron Transport Complex III; D010100:Oxygen