Mitochondria and cell death: outer membrane permeabilization and beyond - PubMed (original) (raw)
Review
doi: 10.1038/nrm2952. Epub 2010 Aug 4.
Affiliations
- PMID: 20683470
- DOI: 10.1038/nrm2952
Review
Mitochondria and cell death: outer membrane permeabilization and beyond
Stephen W G Tait et al. Nat Rev Mol Cell Biol. 2010 Sep.
Abstract
Mitochondrial outer membrane permeabilization (MOMP) is often required for activation of the caspase proteases that cause apoptotic cell death. Various intermembrane space (IMS) proteins, such as cytochrome c, promote caspase activation following their mitochondrial release. As a consequence, mitochondrial outer membrane integrity is highly controlled, primarily through interactions between pro- and anti-apoptotic members of the B cell lymphoma 2 (BCL-2) protein family. Following MOMP by pro-apoptotic BCL-2-associated X protein (BAX) or BCL-2 antagonist or killer (BAK), additional regulatory mechanisms govern the mitochondrial release of IMS proteins and caspase activity. MOMP typically leads to cell death irrespective of caspase activity by causing a progressive decline in mitochondrial function, although cells can survive this under certain circumstances, which may have pathophysiological consequences.
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