title: Mature DIABLO/Smac is produced by the IMP protease complex on the mitochondrial inner membrane.
abstract: DIABLO/Smac is a mitochondrial protein that can promote apoptosis by promoting the release and activation of caspases. To do so, DIABLO/Smac must first be processed by a mitochondrial protease and then released into the cytosol, and we show this in an intact cellular system. We propose that the precursor form of DIABLO/Smac enters the mitochondria through a stop-transfer pathway and is processed to its active form by the inner membrane peptidase (IMP) complex. Catalytic subunits of the mammalian IMP complex were identified based on sequence conservation and functional complementation, and the novel sequence motif RX(5)P in Imp1 and NX(5)S in Imp2 distinguish the two catalytic subunits. DIABLO/Smac is one of only a few specific proteins identified as substrates for the IMP complex in the mitochondrial intermembrane space.
authors.affiliation: Russell Grimwade School of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Lena
authors.initials: L
authors.lastname: Burri
authors.forename: Yvan
authors.initials: Y
authors.lastname: Strahm
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Hawkins
authors.forename: Ian E
authors.initials: IE
authors.lastname: Gentle
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Puryer
authors.forename: Anne
authors.initials: A
authors.lastname: Verhagen
authors.forename: Bernard
authors.initials: B
authors.lastname: Callus
authors.forename: David
authors.initials: D
authors.lastname: Vaux
authors.forename: Trevor
authors.initials: T
authors.lastname: Lithgow
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D015153:Blotting, Western; D020134:Catalytic Domain; D017124:Conserved Sequence; D010450:Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007425:Intracellular Membranes / Q000201:enzymology* / Q000378:metabolism*; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis*; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins; D010450:Endopeptidases