Cited by 18Cell death mechanisms and regulationLipid Membrane Structure and BehaviorMitochondrial Function and Pathology

Integration and Oligomerization of Bax Protein in Lipid Bilayers Characterized by Single Molecule Fluorescence Study

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Luo, Lu, Yang, Jun, Liu, Dongxiang·2014·Journal of Biological Chemistry

Abstract

Bax is a pro-apoptotic Bcl-2 family protein. The activated Bax translocates to mitochondria, where it forms pore and permeabilizes the mitochondrial outer membrane. This process requires the BH3-only activator protein (i.e. tBid) and can be inhibited by anti-apoptotic Bcl-2 family proteins such as Bcl-xL. Here by using single molecule fluorescence techniques, we studied the integration and oligomerization of Bax in lipid bilayers. Our study revealed that Bax can bind to lipid membrane spontaneously in the absence of tBid. The Bax pore formation undergoes at least two steps: pre-pore formation and membrane insertion. The activated Bax triggered by tBid or BH3 domain peptide integrates on bilayers and tends to form tetramers, which are termed as pre-pore. Subsequent insertion of the pre-pore into membrane is highly dependent on the composition of cardiolipin in lipid bilayers. Bcl-xL can translocate Bax from membrane to solution and inhibit the pore formation. The study of Bax integration and oligomerization at the single molecule level provides new evidences that may help elucidate the pore formation of Bax and its regulatory mechanism in apoptosis.

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Crossref · 10.1074/jbc.m114.583393

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Authors
Luo, L., Yang, J., & Liu, D.
Affiliations
  • Chinese Academy of Sciences (CN)
  • Shanghai Institute of Planned Parenthood Research (CN)
Corresponding author
Liu, Dongxiang
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2014-11
Volume
289
Issue
46
Pages
31708-31718
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2017453569
Cited by
18
References
35
Citations by year
2026: 1 · 2025: 2 · 2024: 2 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 1
FWCI
0.68
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
Bax, Bcl-2 family proteins, mitochondrial outer membrane permeabilization, pore formation, oligomerization, tBid, BH3 domain, Bcl-xL, cardiolipin, apoptosis, membrane insertion
MeSH terms
Bcl-2-Like Protein 11, Cardiolipins, Cell Membrane, Gene Expression Regulation, Humans, Lipid Bilayers, Membrane Proteins, Mitochondria, Protein Binding, Proto-Oncogene Proteins, Recombinant Proteins, Apoptosis, Protein Structure, Tertiary, Fluorescence Resonance Energy Transfer, bcl-2 Homologous Antagonist-Killer Protein, Apoptosis Regulatory Proteins, bcl-X Protein, BH3 Interacting Domain Death Agonist Protein, bcl-2-Associated X Protein

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