{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:42:08Z","timestamp":1773290528082,"version":"3.50.1"},"reference-count":50,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2001,6,1]],"date-time":"2001-06-01T00:00:00Z","timestamp":991353600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2001,6,1]],"date-time":"2001-06-01T00:00:00Z","timestamp":991353600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001588","name":"Enterprise Ireland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001588","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010414","name":"Health Research Board","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010414","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmn.com","cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Trends in Biochemical Sciences"],"published-print":{"date-parts":[[2001,6]]},"DOI":"10.1016\/s0968-0004(01)01844-8","type":"journal-article","created":{"date-parts":[[2002,7,25]],"date-time":"2002-07-25T14:37:27Z","timestamp":1027607847000},"page":"390-397","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":398,"title":["The mitochondrial apoptosome: a killer unleashed by the cytochrome seas"],"prefix":"10.1016","volume":"26","author":[{"given":"Colin","family":"Adrain","sequence":"first","affiliation":[]},{"given":"Seamus J","family":"Martin","sequence":"additional","affiliation":[]}],"member":"78","reference":[{"key":"10.1016\/S0968-0004(01)01844-8_BIB1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S0092-8674(00)81873-5","article-title":"Programmed celldeath in animal development","volume":"88","author":"Jacobson","year":"1997","journal-title":"Cell"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB2","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1038\/35037722","article-title":"Corpse clearance defines the meaning of cell death","volume":"407","author":"Savill","year":"2000","journal-title":"Nature"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB3","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/0092-8674(95)90422-0","article-title":"Protease activation during apoptosis: death by a thousand cuts?","volume":"82","author":"Martin","year":"1995","journal-title":"Cell"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB4","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1146\/annurev.biochem.68.1.383","article-title":"Mammalian caspases: structure, activation, substrates and functions during apoptosis","volume":"68","author":"Earnshaw","year":"1999","journal-title":"Annu. Rev. Biochem."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB5","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/35037728","article-title":"CD95's deadly missioninthe immune system","volume":"407","author":"Krammer","year":"2000","journal-title":"Nature"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB6","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1126\/science.281.5381.1309","article-title":"Mitochondria and apoptosis","volume":"281","author":"Green","year":"1998","journal-title":"Science"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB7","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0092-8674(00)80085-9","article-title":"Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c","volume":"86","author":"Liu","year":"1996","journal-title":"Cell"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB8","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1126\/science.275.5303.1132","article-title":"The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis","volume":"275","author":"Kluck","year":"1997","journal-title":"Science"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB9","doi-asserted-by":"crossref","first-page":"22686","DOI":"10.1074\/jbc.274.32.22686","article-title":"Caspase activation involvesthe formation of the apoptosome, a large (approximately 700 kDa) caspase-activating complex","volume":"274","author":"Cain","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB10","doi-asserted-by":"crossref","first-page":"11549","DOI":"10.1074\/jbc.274.17.11549","article-title":"An APAF-1-cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9","volume":"274","author":"Zou","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB11","doi-asserted-by":"crossref","first-page":"17941","DOI":"10.1074\/jbc.274.25.17941","article-title":"Cytochrome c and dATP-mediated oligomerization of Apaf-1 is a prerequisite for procaspase-9 activation","volume":"274","author":"Saleh","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB12","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1101\/gad.13.24.3179","article-title":"Caspase-9 and APAF-1 form an active holoenzyme","volume":"13","author":"Rodriguez","year":"1999","journal-title":"Genes Dev."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB13","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/S0167-5699(97)80014-X","article-title":"Mitochondrial control of apoptosis","volume":"18","author":"Kroemer","year":"1997","journal-title":"Immunol. Today"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB14","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/S0168-9525(98)01573-X","article-title":"Genetics of programmed cell death in C. elegans: past, present and future","volume":"14","author":"Metzstein","year":"1998","journal-title":"Trends Genet."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB15","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1126\/science.275.5303.1122","article-title":"Interaction of CED-4 with CED-3 and CED-9: a molecular framework for cell death","volume":"275","author":"Chinnaiyan","year":"1997","journal-title":"Science"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB16","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1126\/science.275.5303.1126","article-title":"Interaction and regulation of subcellular localization of CED-4 by CED-9","volume":"275","author":"Wu","year":"1997","journal-title":"Science"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB17","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1126\/science.287.5457.1485","article-title":"Translocation of C.elegans CED-4 to nuclear membranes during programmed cell death","volume":"287","author":"Chen","year":"2000","journal-title":"Science"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB18","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S0092-8674(00)81182-4","article-title":"The C.elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9","volume":"93","author":"Conradt","year":"1998","journal-title":"Cell"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB19","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1126\/science.281.5381.1355","article-title":"Essential role of CED-4 oligomerization in CED-3 activation and apoptosis","volume":"281","author":"Yang","year":"1998","journal-title":"Science"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB20","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S0092-8674(00)80501-2","article-title":"Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3","volume":"90","author":"Zou","year":"1997","journal-title":"Cell"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB21","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1084\/jem.181.5.1661","article-title":"Reduction in mitochondrial potential constitutes an early irreversible step of programmed lymphocyte death in vivo","volume":"181","author":"Zamzami","year":"1995","journal-title":"J. Exp. Med."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB22","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/emboj\/17.1.37","article-title":"Mitochondrial cytochrome c release in apoptosis occurs upstream of DEVD-specific caspase activation and independently of mitochondrial transmembrane depolarization","volume":"17","author":"Bossy-Wetzel","year":"1998","journal-title":"EMBO J."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB23","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/35004029","article-title":"The coordinate release of cytochrome c during apoptosis is rapid, complete and kinetically invariant","volume":"2","author":"Goldstein","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB24","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1101\/gad.13.15.1899","article-title":"BCL-2 family members and the mitochondria in apoptosis","volume":"13","author":"Gross","year":"1999","journal-title":"Genes Dev."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB25","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1101\/gad.14.16.2060","article-title":"tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c","volume":"14","author":"Wei","year":"2000","journal-title":"Genes Dev."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB26","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1083\/jcb.144.5.891","article-title":"Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis","volume":"144","author":"Desagher","year":"1999","journal-title":"J. Cell Biol."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB27","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/35019596","article-title":"BAX-dependent transport of cytochrome c reconstituted in pure liposomes","volume":"2","author":"Saito","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB28","doi-asserted-by":"crossref","first-page":"8461","DOI":"10.1074\/jbc.275.12.8461","article-title":"Expression and functional analysis of Apaf-1 isoforms. Extra Wd-40 repeat is required for cytochrome c bindingand regulated activation of procaspase-9","volume":"275","author":"Benedict","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB29","doi-asserted-by":"crossref","first-page":"33489","DOI":"10.1074\/jbc.273.50.33489","article-title":"WD-40 repeat region regulates Apaf-1 self-association and procaspase-9 activation","volume":"273","author":"Hu","year":"1998","journal-title":"J. Biol. Chem."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB30","doi-asserted-by":"crossref","first-page":"20855","DOI":"10.1074\/jbc.274.30.20855","article-title":"Regulation of apoptotic protease activating factor-1 oligomerization and apoptosis by the WD-40 repeat region","volume":"274","author":"Adrain","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB31","doi-asserted-by":"crossref","first-page":"3586","DOI":"10.1093\/emboj\/18.13.3586","article-title":"Role of cytochrome c and dATP\/ATP hydrolysis in Apaf-1-mediated caspase-9 activation and apoptosis","volume":"18","author":"Hu","year":"1999","journal-title":"EMBO J."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB32","doi-asserted-by":"crossref","first-page":"31199","DOI":"10.1074\/jbc.C000405200","article-title":"Cytochrome c promotes caspase-9 activation by inducing nucleotide binding to Apaf-1","volume":"275","author":"Jiang","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB33","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/S1097-2765(00)80095-7","article-title":"Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization","volume":"1","author":"Srinivasula","year":"1998","journal-title":"Mol. Cell"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB34","doi-asserted-by":"crossref","first-page":"6067","DOI":"10.1074\/jbc.275.9.6067","article-title":"Apaf-1 oligomerizes into biologically active approximately 700-kDa and inactive approximately 1.4-MDa apoptosome complexes","volume":"275","author":"Cain","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB35","doi-asserted-by":"crossref","first-page":"8359","DOI":"10.1074\/jbc.274.13.8359","article-title":"Caspase-9 can be activated without proteolytic processing","volume":"274","author":"Stennicke","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB36","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/35065125","article-title":"A conserved XIAP-interaction motif in caspase-9 and Smac\/Diablo regulates caspase activity and apoptosis","volume":"410","author":"Srinivasula","year":"2001","journal-title":"Nature"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB37","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1083\/jcb.149.3.623","article-title":"Pro-apoptotic apoptosis protease-activating factor 1 (Apaf-1) has a cytoplasmic localization distinct from Bcl-2 or Bcl-XL","volume":"149","author":"Hausmann","year":"2000","journal-title":"J. Cell. Biol."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB38","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/35019501","article-title":"Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome","volume":"2","author":"Beere","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB39","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/35019510","article-title":"Negative regulation of the Apaf-1 apoptosome by Hsp70","volume":"2","author":"Saleh","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB40","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/40901","article-title":"X-linked IAP is a direct inhibitor of cell-death proteases","volume":"388","author":"Deveraux","year":"1997","journal-title":"Nature"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB41","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1093\/emboj\/17.8.2215","article-title":"IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases","volume":"17","author":"Deveraux","year":"1998","journal-title":"EMBO J."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB42","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1126\/science.288.5467.874","article-title":"Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli","volume":"288","author":"Yang","year":"2000","journal-title":"Science"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB43","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0092-8674(00)00008-8","article-title":"Smac, a mitochondrial protein that promotes cytochrome c dependent caspase activation by eliminating IAP inhibition","volume":"102","author":"Du","year":"2000","journal-title":"Cell"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB44","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0092-8674(00)00009-X","article-title":"Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins","volume":"102","author":"Verhagen","year":"2000","journal-title":"Cell"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB45","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1038\/35050012","article-title":"Structural basis of IAP recognition by Smac\/Diablo","volume":"408","author":"Wu","year":"2000","journal-title":"Nature"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB46","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1038\/35050006","article-title":"Structural basis for binding of Smac\/Diablo to the XIAP BIR3 domain","volume":"408","author":"Liu","year":"2000","journal-title":"Nature"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB47","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1083\/jcb.144.2.281","article-title":"Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner","volume":"144","author":"Slee","year":"1999","journal-title":"J. Cell. Biol."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB48","doi-asserted-by":"crossref","first-page":"7320","DOI":"10.1074\/jbc.M008363200","article-title":"Executioner caspases -3, -6 and -7 perform distinct, non-redundant roles during the demolition phase of apoptosis","volume":"276","author":"Slee","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/S0968-0004(01)01844-8_BIB49","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0092-8674(00)81477-4","article-title":"Differential requirement for caspase-9 in apoptotic pathways in vivo","volume":"94","author":"Hakem","year":"1998","journal-title":"Cell"},{"key":"10.1016\/S0968-0004(01)01844-8_BIB50","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/17135","article-title":"Molecular characterization of mitochondrial apoptosis-inducing factor","volume":"397","author":"Susin","year":"1999","journal-title":"Nature"}],"container-title":["Trends in Biochemical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968000401018448?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968000401018448?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T21:35:47Z","timestamp":1760823347000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0968000401018448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,6]]},"references-count":50,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2001,6]]}},"alternative-id":["S0968000401018448"],"URL":"https:\/\/doi.org\/10.1016\/s0968-0004(01)01844-8","relation":{},"ISSN":["0968-0004"],"issn-type":[{"value":"0968-0004","type":"print"}],"subject":[],"published":{"date-parts":[[2001,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The mitochondrial apoptosome: a killer unleashed by the cytochrome seas","name":"articletitle","label":"Article Title"},{"value":"Trends in Biochemical Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/S0968-0004(01)01844-8","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"converted-article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2001 Elsevier Science Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}