Cited by 174Cell death mechanisms and regulationMitochondrial Function and PathologyCardiac Ischemia and Reperfusion

BAX unleashed: the biochemical transformation of an inactive cytosolic monomer into a toxic mitochondrial pore

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Walensky, Loren D., Gavathiotis, Evripidis·2011·Trends in Biochemical Sciences

Abstract

BAX, the BCL-2-associated X protein, is a cardinal proapoptotic member of the BCL-2 family, which regulates the critical balance between cellular life and death. Because so many medical conditions can be categorized as diseases of either too many or too few cells, dissecting the biochemistry of BCL-2 family proteins and developing pharmacological strategies to target them have become high priority scientific objectives. Here, we focus on BAX, a latent, cytosolic and monomeric protein that transforms into a lethal mitochondrial oligomer in response to cellular stress. New insights into the structural location of BAX's 'on switch', and the multi-step conformational changes that ensue upon BAX activation, are providing fresh opportunities to modulate BAX for potential benefit in human diseases characterized by pathologic cell survival or unwanted cellular demise.

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Authors
Walensky, L. D., & Gavathiotis, E.
Affiliations
  • Boston Children's Hospital (US)
  • Albert Einstein College of Medicine (US)
Corresponding author
  • Walensky, Loren D.
  • Gavathiotis, Evripidis
Venue
Trends in Biochemical Sciences
Publisher
Elsevier BV
Published
2011-12
Volume
36
Issue
12
Pages
642-652
ISSN
0968-0004 (ISSN-L)
OpenAlex
W1986722992
Cited by
173
References
119
Citations by year
2026: 9 · 2025: 7 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 9 · 2020: 8 · 2019: 9 · 2018: 14 · 2017: 12 · 2016: 14 · 2015: 14 · 2014: 21 · 2013: 27 · 2012: 12
FWCI
1.74
Type
journal article
Language
en
Open access
Locations
  • Trends in Biochemical Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R00HL095929, K99HL095929)
  • National Cancer Institute (R01CA050239, 5R01CA50239)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
Keywords
Bax, Bcl-2 family proteins, apoptosis, Bax oligomerization, conformational change, Bax activation, cell death regulation
MeSH terms
Animals, Cytosol, Humans, Mitochondria, Models, Molecular, Apoptosis, bcl-2-Associated X Protein

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