Mature DIABLO/Smac is produced by the IMP protease complex on the mitochondrial inner membrane.
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.
Burri
Lena
L
Russell Grimwade School of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC 3010, Australia.
Strahm
Yvan
Y
Hawkins
Christine J
CJ
Gentle
Ian E
IE
Puryer
Michelle A
MA
Verhagen
Anne
A
Callus
Bernard
B
Vaux
David
D
Lithgow
Trevor
T
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
D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins; D010450:Endopeptidases