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

Wei Xing Zong, Chi Li, Georgia Hatzivassiliou, Tullia Lindsten, Qian Chun Yu, Junying Yuan, Craig B. Thompson

Research output: Contribution to journalArticlepeer-review

471 Scopus citations


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 bak-/-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.

Original languageEnglish (US)
Pages (from-to)59-69
Number of pages11
JournalJournal of Cell Biology
Issue number1
StatePublished - Jul 7 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology


  • Bak
  • Bax
  • Ca
  • Caspase 12
  • ER

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