BH3-only protein BIM mediates heat shock-induced apoptosis

Indra M. Mahajan, Miao Der Chen, Israel Muro, John D. Robertson, Casey Wright, Shawn B. Bratton

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Acute heat shock can induce apoptosis through a canonical pathway involving the upstream activation of caspase-2, followed by BID cleavage and stimulation of the intrinsic pathway. Herein, we report that the BH3-only protein BIM, rather than BID, is essential to heat shock-induced cell death. We observed that BIM-deficient cells were highly resistant to heat shock, exhibiting short and long-term survival equivalent to Bax-/-Bak-/- cells and better than either Bid-/- or dominant-negative caspase-9-expressing cells. Only Bim-/- and Bax-/-Bak-/- cells exhibited resistance to mitochondrial outer membrane permeabilization and loss of mitochondrial inner membrane potential. Moreover, while dimerized caspase-2 failed to induce apoptosis in Bid-/- cells, it readily did so in Bim-/- cells, implying that caspase-2 kills exclusively through BID, not BIM. Finally, BIM reportedly associates with MCL-1 following heat shock, and Mcl-1-/- cells were indeed sensitized to heat shock-induced apoptosis. However, pharmacological inhibition of BCL-2 and BCL-XL with ABT-737 also sensitized cells to heat shock, most likely through liberation of BIM. Thus, BIM mediates heat shock-induced apoptosis through a BAX/BAK-dependent pathway that is antagonized by antiapoptotic BCL-2 family members.

Original languageEnglish (US)
Article numbere84388
JournalPLoS One
Volume9
Issue number1
DOIs
StatePublished - Jan 10 2014
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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  • Cite this

    Mahajan, I. M., Chen, M. D., Muro, I., Robertson, J. D., Wright, C., & Bratton, S. B. (2014). BH3-only protein BIM mediates heat shock-induced apoptosis. PLoS One, 9(1), [e84388]. https://doi.org/10.1371/journal.pone.0084388