Cited by 82Mitochondrial Function and PathologyCell death mechanisms and regulationAutophagy in Disease and Therapy

Respiratory chain complex II as general sensor for apoptosis

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Grimm, Stefan·2013·Biochimica et Biophysica Acta (BBA) - Bioenergetics

Abstract

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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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
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

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