| Regulation of the intrinsic apoptosis pathway by reactive oxygen species. | |
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MedLine Citation:
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PMID: 22978471 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Significance: 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. Recent Advances: 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 (Apaf-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 posttranslational modification, including proteolysis, phosphorylation, and in some cases, direct oxidative modification. Critical Issues: 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. Future Directions: 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. |
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Authors:
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Chu-Chiao Wu; Shawn B Bratton |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-9-16 |
Journal Detail:
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Title: Antioxidants & redox signaling Volume: - ISSN: 1557-7716 ISO Abbreviation: Antioxid. Redox Signal. Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-9-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100888899 Medline TA: Antioxid Redox Signal Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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M.D. Anderson Cancer Center, Molecular Carcinogenesis, Smithville, Texas, United States; CWu8@mdanderson.org. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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