title: AAA proteases with catalytic sites on opposite membrane surfaces comprise a proteolytic system for the ATP-dependent degradation of inner membrane proteins in mitochondria.
abstract: The mechanism of selective protein degradation of membrane proteins in mitochondria has been studied employing a model protein that is subject to rapid proteolysis within the inner membrane. Protein degradation was mediated by two different proteases: (i) the m-AAA protease, a protease complex consisting of multiple copies of the ATP-dependent metallopeptidases Yta1Op (Afg3p) and Yta12p (Rcalp); and (ii) by Ymelp (Ytallp) that also is embedded in the inner membrane. Ymelp, highly homologous to Yta1Op and Yta12p, forms a complex of approximately 850 kDa in the inner membrane and exerts ATP-dependent metallopeptidase activity. While the m-AAA protease exposes catalytic sites to the mitochondrial matrix, Ymelp is active in the intermembrane space. The Ymelp complex was therefore termed 'i-AAA protease'. Analysis of the proteolytic fragments indicated cleavage of the model polypeptide at the inner and outer membrane surface and within the membrane-spanning domain. Thus, two AAA proteases with their catalytic sites on opposite membrane surfaces constitute a novel proteolytic system for the degradation of membrane proteins in mitochondria.
authors.affiliation: Institut für Physiologische Chemie der Universität München, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Leonhard
authors.forename: J M
authors.initials: JM
authors.lastname: Herrmann
authors.forename: R A
authors.initials: RA
authors.lastname: Stuart
authors.forename: G
authors.initials: G
authors.lastname: Mannhaupt
authors.forename: W
authors.initials: W
authors.lastname: Neupert
authors.forename: T
authors.initials: T
authors.lastname: Langer
mesh_terms: D049069:ATP-Dependent Proteases; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000502:physiology*; D001665:Binding Sites; D003576:Electron Transport Complex IV / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008666:Metalloendopeptidases; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins; D016297:Mutagenesis, Site-Directed; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D013762:Tetrahydrofolate Dehydrogenase; D003576:Electron Transport Complex IV; D049069:ATP-Dependent Proteases; C082702:YME1 protein, S cerevisiae; D008666:Metalloendopeptidases; D000251:Adenosine Triphosphatases; C102166:YTA12 protein, S cerevisiae; C090045:AFG3 protein, S cerevisiae