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

11 Citations (Scopus)

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

Fingerprint

heat stress
Shock
apoptosis
Hot Temperature
Apoptosis
Caspase 2
caspase-2
Proteins
proteins
cells
Membranes
Caspase 9
caspase-9
Cell death
Bcl-2-Like Protein 11
Mitochondrial Membrane Potential
Mitochondrial Membranes
membrane potential
cell death
Chemical activation

ASJC Scopus subject areas

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

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

BH3-only protein BIM mediates heat shock-induced apoptosis. / Mahajan, Indra M.; Chen, Miao Der; Muro, Israel; Robertson, John D.; Wright, Casey; Bratton, Shawn B.

In: PLoS One, Vol. 9, No. 1, e84388, 10.01.2014.

Research output: Contribution to journalArticle

Mahajan, IM, Chen, MD, Muro, I, Robertson, JD, Wright, C & Bratton, SB 2014, 'BH3-only protein BIM mediates heat shock-induced apoptosis', PLoS One, vol. 9, no. 1, e84388. https://doi.org/10.1371/journal.pone.0084388
Mahajan IM, Chen MD, Muro I, Robertson JD, Wright C, Bratton SB. BH3-only protein BIM mediates heat shock-induced apoptosis. PLoS One. 2014 Jan 10;9(1). e84388. https://doi.org/10.1371/journal.pone.0084388
Mahajan, Indra M. ; Chen, Miao Der ; Muro, Israel ; Robertson, John D. ; Wright, Casey ; Bratton, Shawn B. / BH3-only protein BIM mediates heat shock-induced apoptosis. In: PLoS One. 2014 ; Vol. 9, No. 1.
@article{abf3fc75ac7745e3bb0606ce72c2373c,
title = "BH3-only protein BIM mediates heat shock-induced apoptosis",
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.",
author = "Mahajan, {Indra M.} and Chen, {Miao Der} and Israel Muro and Robertson, {John D.} and Casey Wright and Bratton, {Shawn B.}",
year = "2014",
month = "1",
day = "10",
doi = "10.1371/journal.pone.0084388",
language = "English (US)",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - BH3-only protein BIM mediates heat shock-induced apoptosis

AU - Mahajan, Indra M.

AU - Chen, Miao Der

AU - Muro, Israel

AU - Robertson, John D.

AU - Wright, Casey

AU - Bratton, Shawn B.

PY - 2014/1/10

Y1 - 2014/1/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84897512065&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897512065&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0084388

DO - 10.1371/journal.pone.0084388

M3 - Article

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

M1 - e84388

ER -