Respiratory chain complex II as general sensor for apoptosis
Open accessAbstract
I review here the evidence that complex II of the respiratory chain (RC) constitutes a general sensor for apoptosis induction. This concept emerged from work on neurodegenerative diseases and from recent data on metabolic alterations in cancer cells affecting the RC and in particular on mutations of complex II subunits. It is also supported by experiments with many anticancer compounds that compared the apoptosis sensitivities of complex II-deficient versus WT cells. These results are explained by the mechanistic understanding of how complex II mediates the diverse range of apoptosis signals. This protein aggregate is specifically activated for apoptosis by pH change as a common and early feature of dying cells. This leads to the dissociation of its SDHA and SDHB subunits from the remaining membrane-anchored subunits and the consequent block of it enzymatic SQR activity, while its SDH activity, which is contained in the SDHA/SDHB subcomplex, remains intact. The uncontrolled SDH activity then generates excessive amounts of reactive oxygen species for the demise of the cell. Future studies on these mitochondrial processes will help refine this model, unravel the contribution of mutations in complex II subunits as the cause of degenerative neurological diseases and tumorigenesis, and aid in discovering novel interference options. This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease.
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CII has emerged as an important factor in cell death induction.
“Beyond bioenergetics, CII has emerged as an important factor in cell death induction.11,12”
From Ubiquinone-binding site mutagenesis reveals the role of mitochondrial complex II in cell death initiation (2015) · cites this paper as [12]
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- Authors
- Grimm, S.
- Affiliations
- Imperial College London (GB)
- Corresponding author
- Grimm, Stefan
- Venue
- Biochimica et Biophysica Acta (BBA) - Bioenergetics
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 1827
- Issue
- 5
- Pages
- 565-572
- ISSN
- 0005-2728 (ISSN-L)
- OpenAlex
- W2053421970
- Cited by
- 82
- References
- 109
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 7 · 2020: 4 · 2019: 13 · 2018: 7 · 2017: 6 · 2016: 6 · 2015: 9 · 2014: 10 · 2013: 1
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Bioenergetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Breast Cancer Campaign
- Medical Research Council
- Cancer Research UK
- Wellcome Trust
- 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
- respiratory chain complex II, apoptosis, succinate dehydrogenase, SDHA, SDHB, reactive oxygen species, neurodegenerative diseases, cancer metabolism, anticancer agents, apoptosis signaling
- MeSH terms
- Electron Transport, Humans, Hydrogen-Ion Concentration, Models, Biological, Mutation, Succinate Dehydrogenase, Apoptosis, Reactive Oxygen Species, Electron Transport Complex II
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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