Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis

  • Wei-Xing Zong
    1Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104
  • Chi Li
    1Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104
  • Georgia Hatzivassiliou
    1Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104
  • Tullia Lindsten
    2Department of Pathology and Laboratory Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104
  • Qian-Chun Yu
    2Department of Pathology and Laboratory Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104
  • Junying Yuan
    3Department of Cell Biology, Harvard Medical School, Boston, MA 02115
  • Craig B. Thompson
    1Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104

書誌事項

公開日
2003-07-07
DOI
  • 10.1083/jcb.200302084
公開者
Rockefeller University Press

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説明

<jats:p>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.</jats:p>

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