Dynamics of nucleoid structure regulated by mitochondrial fission contributes to cristae reformation and release of cytochrome c
Open accessAbstract
Mammalian cells typically contain thousands of copies of mitochondrial DNA assembled into hundreds of nucleoids. Here we analyzed the dynamic features of nucleoids in terms of mitochondrial membrane dynamics involving balanced fusion and fission. In mitochondrial fission GTPase dynamin-related protein (Drp1)-deficient cells, nucleoids were enlarged by their clustering within hyperfused mitochondria. In normal cells, mitochondrial fission often occurred adjacent to nucleoids, since localization of Mff and Drp1 is dependent on the nucleoids. Thus, mitochondrial fission adjacent to nucleoids should prevent their clustering by maintaining small and fragmented nucleoids. The enhanced clustering of nucleoids resulted in the formation of highly stacked cristae structures in enlarged bulb-like mitochondria (mito-bulbs). Enclosure of proapoptotic factor cytochrome c, but not of Smac/DIABLO, into the highly stacked cristae suppressed its release from mitochondria under apoptotic stimuli. In the absence of nucleoids, Drp1 deficiency failed to form mito-bulbs and to protect against apoptosis. Thus, mitochondrial dynamics by fission and fusion play a critical role in controlling mitochondrial nucleoid structures, contributing to cristae reformation and the proapoptotic status of mitochondria.
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Mitochondrial fission is involved in the release of cytochrome C from mitochondria, which acts as a scavenger of ROS in the cytosol.
“Mitochondrial fission has been reported to be involved in the release of cytochrome C from mitochondria, which acts as a scavenger of ROS in the cytosol [48].”
From In Candida glabrata, ERMES Component GEM1 Controls Mitochondrial Morphology, mtROS, and Drug Efflux Pump Expression, Resulting in Azole Susceptibility (2023) · cites this paper as [48]
The Discussion states that Drp1-dependent mitochondrial fission facilitates cytochrome c release during apoptosis. The paper does not say that released cytochrome c scavenges ROS in the cytosol; its Discussion mentions ROS only in relation to neuronal sensitivity to apoptosis. (LLM, conf=0.88)
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- Authors
- Ban-Ishihara, R., Ishihara, T., Sasaki, N., Mihara, K., & Ishihara, N.
- Affiliations
- Kurume University (JP)
- Nagoya University (JP)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-07-02
- Volume
- 110
- Issue
- 29
- Pages
- 11863-11868
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3718159
- OpenAlex
- W2033275867
- Cited by
- 231
- References
- 34
- Citations by year
- 2026: 15 · 2025: 14 · 2024: 21 · 2023: 19 · 2022: 16 · 2021: 22 · 2020: 24 · 2019: 23 · 2018: 14 · 2017: 11 · 2016: 15 · 2015: 14 · 2014: 16 · 2013: 5
- FWCI
- 7.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Takeda Science Foundation
- Fukuoka Foundation for Sound Health
- Japan Society for the Promotion of Science (24770133, 23570076)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- mitochondrial nucleoids, mitochondrial fission, mitochondrial fusion, Drp1, Mff, cytochrome c release, Smac/DIABLO, apoptosis, mitochondrial DNA
- MeSH terms
- Diamines, Fluorescent Antibody Technique, HeLa Cells, Humans, Microscopy, Fluorescence, Mitochondria, Organic Chemicals, Oxygen Consumption, Quinolines, Immunoblotting, Apoptosis, Reverse Transcriptase Polymerase Chain Reaction, Dynamins, RNA Interference, RNA, Small Interfering, Cytochromes c, Microscopy, Electron, Transmission, Mitochondrial Membranes, Benzothiazoles, Time-Lapse Imaging, Mitochondrial Dynamics
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