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PMID:12847083
| Citation |
Zong, WX, Li, C, Hatzivassiliou, G, Lindsten, T, Yu, QC, Yuan, J and Thompson, CB (2003) Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis. J. Cell Biol. 162:59-69 |
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| Abstract |
Bax and Bak play a redundant but essential role in apoptosis initiated by the mitochondrial release of apoptogenic factors. In addition to their presence at the mitochondrial outer membrane, Bax and Bak can also localize to the ER. Agents that initiate ER stress responses can induce conformational changes and oligomerization of Bax on the ER as well as on mitochondria. In wild-type cells, this is associated with caspase 12 cleavage that is abolished in bax-/-bak-/- cells. In bax-/-bak-/- cells, introduction of Bak mutants selectively targeted to either mitochondria or the ER can induce apoptosis. However, ER-targeted, but not mitochondria-targeted, Bak leads to progressive depletion of ER Ca2+ and induces caspase 12 cleavage. In contrast, mitochondria-targeted Bak leads to enhanced caspase 7 and PARP cleavage in comparison with the ER-targeted Bak. These findings demonstrate that in addition to their functions at mitochondria, Bax and Bak also localize to the ER and function to initiate a parallel pathway of caspase activation and apoptosis. |
| Links |
PubMed PMC2172724 Online version:10.1083/jcb.200302084 |
| Keywords |
Animals; Apoptosis/physiology; Calcium/metabolism; Calcium Signaling/genetics; Caspase 12; Caspase 7; Caspases/metabolism; Cell Line, Transformed; Endoplasmic Reticulum/metabolism; Endoplasmic Reticulum/ultrastructure; Eukaryotic Cells/metabolism; Eukaryotic Cells/ultrastructure; Membrane Proteins/deficiency; Membrane Proteins/genetics; Mice; Mitochondria/genetics; Mitochondria/metabolism; Mutation/genetics; Poly(ADP-ribose) Polymerases/metabolism; Protein Conformation; Protein Transport/genetics; Proto-Oncogene Proteins/deficiency; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins c-bcl-2; Stress, Physiological/genetics; Stress, Physiological/metabolism; bcl-2 Homologous Antagonist-Killer Protein; bcl-2-Associated X Protein |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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See also
References
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