title: Prohibitins interact genetically with Atp23, a novel processing peptidase and chaperone for the F1Fo-ATP synthase.
abstract: The generation of cellular energy depends on the coordinated assembly of nuclear and mitochondrial-encoded proteins into multisubunit respiratory chain complexes in the inner membrane of mitochondria. Here, we describe the identification of a conserved metallopeptidase present in the intermembrane space, termed Atp23, which exerts dual activities during the biogenesis of the F(1)F(O)-ATP synthase. On one hand, Atp23 serves as a processing peptidase and mediates the maturation of the mitochondrial-encoded F(O)-subunit Atp6 after its insertion into the inner membrane. On the other hand and independent of its proteolytic activity, Atp23 promotes the association of mature Atp6 with Atp9 oligomers. This assembly step is thus under the control of two substrate-specific chaperones, Atp10 and Atp23, which act on opposite sides of the inner membrane. Strikingly, both ATP10 and ATP23 were found to genetically interact with prohibitins, which build up large, ring-like assemblies with a proposed scaffolding function in the inner membrane. Our results therefore characterize not only a novel processing peptidase with chaperone activity in the mitochondrial intermembrane space but also link the function of prohibitins to the F(1)F(O)-ATP synthase complex.
authors.affiliation: Institute for Genetics and Center for Molecular Medicine, University of Cologne, D-50674 Cologne, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Osman
authors.forename: Claudia
authors.initials: C
authors.lastname: Wilmes
authors.forename: Takashi
authors.initials: T
authors.lastname: Tatsuta
authors.forename: Thomas
authors.initials: T
authors.lastname: Langer
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000201:enzymology; D017353:Gene Deletion; D005804:Genes, Lethal; D045726:Metalloproteases / Q000032:analysis; D008928:Mitochondria / Q000201:enzymology; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D000091402:Prohibitins; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000378:metabolism
chemical_list: C501004:ATP6 protein, S cerevisiae; C486885:Atp10 protein, S cerevisiae; D018832:Molecular Chaperones; D000091402:Prohibitins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C519195:ATP23 protein, S cerevisiae; D045726:Metalloproteases; D010447:Peptide Hydrolases; C474451:F1F0-ATP synthase; D025261:Mitochondrial Proton-Translocating ATPases