title: Cardiolipin defines the interactome of the major ADP/ATP carrier protein of the mitochondrial inner membrane.
abstract: Defined mutations in the mitochondrial ADP/ATP carrier (AAC) are associated with certain types of progressive external ophthalmoplegia. AAC is required for oxidative phosphorylation (OXPHOS), and dysregulation of AAC has been implicated in apoptosis. Little is known about the AAC interactome, aside from a known requirement for the phospholipid cardiolipin (CL) and that it is thought to function as a homodimer. Using a newly developed dual affinity tag, we demonstrate that yeast AAC2 physically participates in several protein complexes of distinct size and composition. The respiratory supercomplex and several smaller AAC2-containing complexes, including other members of the mitochondrial carrier family, are identified here. In the absence of CL, most of the defined interactions are destabilized or undetectable. The absence of CL and/or AAC2 results in distinct yet additive alterations in respiratory supercomplex structure and respiratory function. Thus, a single lipid can significantly alter the functional interactome of an individual protein.
authors.affiliation: Department of Chemistry and Biochemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Claypool
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Oktay
authors.forename: Pinmanee
authors.initials: P
authors.lastname: Boontheung
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Loo
authors.forename: Carla M
authors.initials: CM
authors.lastname: Koehler
mesh_terms: D002308:Cardiolipins / Q000502:physiology*; D019281:Dimerization; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism / Q000502:physiology; D004591:Electrophoresis, Polyacrylamide Gel; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism* / Q000502:physiology; D051336:Mitochondrial Membranes / Q000378:metabolism*; D025941:Protein Interaction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology
chemical_list: D002308:Cardiolipins; D045222:Electron Transport Chain Complex Proteins; C112225:PET9 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000226:Mitochondrial ADP, ATP Translocases
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