Cited by 221Cell death mechanisms and regulationMitochondrial Function and PathologyAutophagy in Disease and Therapy

Activation of mitochondrial protease OMA1 by Bax and Bak promotes cytochrome c release during apoptosis

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Jiang, Xian, Jiang, Hui, Shen, Zhirong, Wang, Xiaodong·2014·Proceedings of the National Academy of Sciences

Abstract

Significance: The release of cytochrome c from its normal intermembrane space in mitochondria marks the initiation of apoptosis in mammalian cells. The process is triggered by the aggregation of B-cell leukemia/lymphoma 2 (BCL2)-associated X (Bax) and BCL2-antagonist/killer (Bak) proteins on the surface of mitochondria. We found that a mitochondrial inner membrane protease, OMA1 (overlapping activity with m -AAA protease), is specifically activated and is responsible for cleaving another inner membrane protein, optical nerve atrophy 1 (OPA1), upon Bax/Bak aggregation. The cleavage of OPA1 triggers the remodeling of mitochondrial cristae, allowing the majority of cytochrome c inside the cristae to be released. This finding provided a more comprehensive understanding of this critical molecular event during apoptosis.

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Crossref · 10.1073/pnas.1417253111

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  • The release of CYCS and SMAC to the cytosol is favored by mitochondrial cristae remodeling, which relies on the oligomerization and activation of OPA1, possibly preceded by BAX-dependent and BAK-dependent activation of OMA1 and/or DRP1.

    “The release of CYCS and SMAC to the cytosol is favored by mitochondrial cristae remodeling [164], which relies on the oligomerization and activation of OPA1, mitochondrial dynamin like GTPase (OPA1) [165], possibly preceded by the BAX-dependent and BAK-dependent activation of OMA1 zinc metallopeptidase (OMA1) [166, 167], and/or dynamin 1 like (DNM1L; best known as DRP1) [168].”

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Authors
Jiang, X., Jiang, H., Shen, Z., & Wang, X.
Affiliations
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
  • National Institute of Biological Sciences, Beijing (CN)
Venue
Proceedings of the National Academy of Sciences
Published
2014-10
Volume
111
Issue
41
Pages
14782-14787
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2080115272
Cited by
220
References
36
Citations by year
2026: 7 · 2025: 17 · 2024: 17 · 2023: 18 · 2022: 21 · 2021: 24 · 2020: 24 · 2019: 24 · 2018: 17 · 2017: 20 · 2016: 18 · 2015: 11 · 2014: 2
FWCI
6.97
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • 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 › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
OMA1, Bax, Bak, cytochrome c release, apoptosis, building information modeling, tBid, OPA1, mitochondrial cristae remodeling, mitochondrial outer membrane permeabilization, Bcl-2 family proteins
MeSH terms
Enzyme Activation, Humans, Metalloendopeptidases, Mitochondria, Apoptosis, GTP Phosphohydrolases, Cytochromes c, Cell Line, Tumor, bcl-2 Homologous Antagonist-Killer Protein, BH3 Interacting Domain Death Agonist Protein, bcl-2-Associated X Protein, Protein Stability, Gene Knockdown Techniques

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