The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Loss of OPA1 Perturbates the Mitochondrial Inner Membrane Structure and Integrity, Leading to Cytochrome c Release and Apoptosis
Open accessAbstract
OPA1 encodes a large GTPase related to dynamins, anchored to the mitochondrial cristae inner membrane, facing the intermembrane space. OPA1 haplo-insufficiency is responsible for the most common form of autosomal dominant optic atrophy (ADOA, MIM165500), a neuropathy resulting from degeneration of the retinal ganglion cells and optic nerve atrophy. Here we show that down-regulation of OPA1 in HeLa cells using specific small interfering RNA (siRNA) leads to fragmentation of the mitochondrial network concomitantly to the dissipation of the mitochondrial membrane potential and to a drastic disorganization of the cristae. These events are followed by cytochrome c release and caspase-dependent apoptotic nuclear events. Similarly, in NIH-OVCAR-3 cells, the OPA1 siRNA induces mitochondrial fragmentation and apoptosis, the latter being inhibited by Bcl2 overexpression. These results suggest that OPA1 is a major organizer of the mitochondrial inner membrane from which the maintenance of the cristae integrity depends. As loss of OPA1 commits cells to apoptosis without any other stimulus, we propose that OPA1 is involved in the cytochrome c sequestration and might be a target for mitochondrial apoptotic effectors. Our results also suggest that abnormal apoptosis is a possible pathophysiological process leading to the retinal ganglion cells degeneration in ADOA patients.
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“Opa1 participates in inner mitochondrial membrane fusion and cristae morphogenesis.”
From Mitochondrial DNA and TLR9 drive muscle inflammation upon Opa1 deficiency (2018) · cites this paper as Olichon et al, 2003
In the citing paper
“A decrease in mitochondrial fusion caused by reduced levels of Opa1 can also influence the progression of cell-death pathways (Lee et al., 2004; Olichon et al., 2003).”
From New insights into the role of mitochondria in aging: mitochondrial dynamics and more (2010) · cites this paper as Olichon et al., 2003
In the citing paper
“Knockdown of Opa1 expression with small interfering RNA (siRNA) results in increased mitochondrial fission and decreased Δψm in HeLa cells, leading to abnormal mitochondrial cristae, mitochondrial fragmentation and the release of cytochrome c (Olichon et al., 2003).”
From New insights into the role of mitochondria in aging: mitochondrial dynamics and more (2010) · cites this paper as Olichon et al., 2003
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Metadata
- Authors
- Olichon, A., Baricault, L., Gas, N., Guillou, E., Valette, A., Belenguer, P., & Lenaers, G.
- Affiliations
- Université Toulouse III - Paul Sabatier (FR)
- Corresponding author
- Belenguer, Pascale
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-03
- Volume
- 278
- Issue
- 10
- Pages
- 7743-7746
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1986996580
- Cited by
- 1,168
- References
- 27
- Citations by year
- 2026: 29 · 2025: 46 · 2024: 38 · 2023: 55 · 2022: 47 · 2021: 64 · 2020: 59 · 2019: 61 · 2018: 50 · 2017: 60 · 2016: 78 · 2015: 61 · 2014: 57 · 2013: 39 · 2012: 61
- FWCI
- 12.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- OPA1, mitochondrial fission, mitochondrial cristae, inner mitochondrial membrane, cytochrome c release, apoptosis, mitochondrial membrane potential, autosomal dominant optic atrophy, Bcl-2, GTPase, retinal ganglion cell death
- MeSH terms
- Cytochrome c Group, Humans, Intracellular Membranes, Microscopy, Electron, Mitochondria, Tumor Cells, Cultured, Apoptosis, GTP Phosphohydrolases
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