Mitochondrial respiratory chain complexes: apoptosis sensors mutated in cancer?

• Published in: Oncogene Vol. 30; no. 38; pp. 3985 - 4003
• Main Authors: Lemarie, A, Grimm, S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.09.2011; Nature Publishing Group
• Subjects: 631/208/737; 631/443/319/333/1465; 631/80/82/23; 692/699/67; Ageing, cell death; Animals; Apoptosis; Biological and medical sciences; Cancer; Cell Biology; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cells; Development and progression; DNA, Mitochondrial - genetics; Electron transport; Electron Transport Complex I - chemistry; Electron Transport Complex I - genetics; Electron Transport Complex I - physiology; Electron Transport Complex II - chemistry; Electron Transport Complex II - genetics; Electron Transport Complex II - physiology; Fundamental and applied biological sciences. Psychology; Genetic aspects; Human Genetics; Humans; Internal Medicine; Medicine; Medicine & Public Health; Mitochondria; Mitochondria - metabolism; Mitochondrial DNA; Molecular and cellular biology; Mutation; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Oncology; Oxidative phosphorylation; pH effects; Phosphorylation; Physiological aspects; Proteinase; Reactive oxygen species; Reactive Oxygen Species - metabolism; review; Reviews; Sensors; United Kingdom; apoptosis; mitochondria; respiratory chain; reactive oxygen species; Respiratory chain; Reactive oxygen species; Mitochondria; Malignant tumor; Carcinogenesis; Cancer; Apoptosis
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2011.167

Mutations in cancer cells affecting subunits of the respiratory chain (RC) indicate a central role of oxidative phosphorylation for tumourigenesis. Recent studies have suggested that such mutations of RC complexes impact apoptosis induction. We review here the evidence for this hypothesis, which in particular emerged from work on how complex I and II mediate signals for apoptosis. Both protein aggregates are specifically inhibited for apoptosis induction through different means by exploiting with protease activation and pH change, two widespread but independent features of dying cells. Nevertheless, both converge on forming reactive oxygen species for the demise of the cell. Investigations into these mitochondrial processes will remain a rewarding area for unravelling the causes of tumourigenesis and for discovering interference options.