title: Apoptosis: checkpoint at the mitochondrial frontier.
abstract: Apoptosis, an evolutionarily conserved form of cell death, requires a regulated program. Central to the apoptotic program is a family of cysteine proteases, known as caspases, that cleave a subset of cellular proteins, resulting in the stereotypic morphological changes of apoptotic cell death. In living cells caspases are present as inactive zymogens and become activated in response to pro-apoptotic stimuli. Mitochondria participate in the activation of caspases by releasing cytochrome c into the cytosol where it binds to the adaptor molecule Apaf-1 (apoptotic protease activating factor 1) and causes its oligomerization. This renders Apaf-1 competent to recruit and activate the cell death initiator caspase, pro-caspase-9. Once caspase-9 is activated, it cleaves and activates downstream cell death effector caspases. Bcl-2, an apoptosis inhibitor localized to mitochondrial outer membranes, prevents cytochrome c release, caspase activation and cell death. This review discusses recent advances on the role of mitochondria and cytochrome c in the central pathway leading to apoptotic cell death.
authors.affiliation: Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA. ella_bossy@liai.org, ebossyw1@san.rr.com
authors.forename: E
authors.initials: E
authors.lastname: Bossy-Wetzel
authors.forename: D R
authors.initials: DR
authors.lastname: Green
mesh_terms: D000818:Animals; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1; D020169:Caspases / Q000378:metabolism; D002474:Cell-Free System; D003574:Cytochrome c Group / Q000502:physiology*; D004272:DNA, Mitochondrial; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D008954:Models, Biological; D011506:Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D014981:Xenopus / Q000378:metabolism
chemical_list: C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D003574:Cytochrome c Group; D004272:DNA, Mitochondrial; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases