A Distinct Pathway Remodels Mitochondrial Cristae and Mobilizes Cytochrome c during Apoptosis
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The mechanism during apoptosis by which cytochrome c is rapidly and completely released in the absence of mitochondrial swelling is uncertain. Here, we show that two distinct pathways are involved. One mediates release of cytochrome c across the outer mitochondrial membrane, and another, characterized in this study, is responsible for the redistribution of cytochrome c stored in intramitochondrial cristae. We have found that the "BH3-only" molecule tBID induces a striking remodeling of mitochondrial structure with mobilization of the cytochrome c stores (approximately 85%) in cristae. This reorganization does not require tBID's BH3 domain and is independent of BAK, but is inhibited by CsA. During this process, individual cristae become fused and the junctions between the cristae and the intermembrane space are opened.
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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].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [164]
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The Incomplete Puzzle of the BCL2 Proteins
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- Authors
- Scorrano, L., Ashiya, M., Buttle, K., Weiler, S., Oakes, S. A., Mannella, C. A., & Korsmeyer, S. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Wadsworth Center (US)
- Corresponding author
- Korsmeyer, Stanley J.
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2002-01
- Volume
- 2
- Issue
- 1
- Pages
- 55-67
- ISSN
- 1534-5807 (ISSN-L)
- OpenAlex
- W2013091489
- Cited by
- 1,072
- References
- 44
- Citations by year
- 2026: 13 · 2025: 40 · 2024: 33 · 2023: 48 · 2022: 26 · 2021: 43 · 2020: 32 · 2019: 53 · 2018: 22 · 2017: 32 · 2016: 39 · 2015: 45 · 2014: 35 · 2013: 44 · 2012: 47
- FWCI
- 21.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 4215 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- National Institutes of Health (32-HL07627-16)
- National Center for Research Resources (01219, 50239-14)
- 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
- apoptosis, cytochrome c release, mitochondrial cristae, tBid, BH3-only proteins, mitochondrial outer membrane, mitochondrial structure, cyclosporine, intermembrane space
- MeSH terms
- Adenylate Kinase, Animals, Carrier Proteins, Cells, Cultured, Cytochrome c Group, Enzyme Inhibitors, Intracellular Membranes, Membrane Proteins, Mice, Inbred BALB C, Microscopy, Electron, Mitochondria, Liver, Mutation, Proto-Oncogene Proteins, Cyclosporine, Apoptosis, Proto-Oncogene Proteins c-bcl-2, bcl-2 Homologous Antagonist-Killer Protein, BH3 Interacting Domain Death Agonist Protein, bcl-2-Associated X Protein, Mice
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