title: Regulation of the intrinsic apoptosis pathway by reactive oxygen species.
abstract: CONCLUSIONS
  The intrinsic apoptosis pathway is conserved from worms to humans and plays a critical role in the normal development and homeostatic control of adult tissues. As a result, numerous diseases from cancer to neurodegeneration are associated with either too little or too much apoptosis.
  
  
  BACKGROUND
  B cell lymphoma-2 (BCL-2) family members regulate cell death, primarily via their effects on mitochondria. In stressed cells, proapoptotic BCL-2 family members promote mitochondrial outer membrane permeabilization (MOMP) and cytochrome c (cyt c) release into the cytoplasm, where it stimulates formation of the "apoptosome." This large, multimeric complex is composed of the adapter protein, apoptotic protease-activating factor-1, and the cysteine protease, caspase-9. Recent studies suggest that proteins involved in the processes leading up to (and including) formation of the apoptosome are subject to various forms of post-translational modification, including proteolysis, phosphorylation, and in some cases, direct oxidative modification.
  
  
  RESULTS
  Despite intense investigation of the intrinsic pathway, significant questions remain regarding how cyt c is released from mitochondria, how the apoptosome is formed and regulated, and how caspase-9 is activated within the complex.
  
  
  CONCLUSIONS
  Further studies on the biochemistry of MOMP and apoptosome formation are needed to understand the mechanisms that underpin these critical processes, and novel animal models will be necessary in the future to ascertain the importance of the many posttranslational modifications reported for BCL-2 family members and components of the apoptosome.
authors.affiliation: Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, USA.
authors.forename: Chu-Chiao
authors.initials: CC
authors.lastname: Wu
authors.forename: Shawn B
authors.initials: SB
authors.lastname: Bratton
mesh_terms: D000818:Animals; D017209:Apoptosis; D053453:Caspase 9 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D051336:Mitochondrial Membranes; D000083162:Mitochondrial Permeability Transition Pore; D018384:Oxidative Stress; D010539:Permeability; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D045304:Cytochromes c; C506433:CASP9 protein, human; D053453:Caspase 9