Abstract
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.
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Acknowledgements
We acknowledge the financial support from Cancer Research UK (to AL and SG) as well as from la Ligue Nationale Contre le Cancer (Hautes-Pyrénées and Haute-Garonne committees; to AL) and support by the Wellcome Trust, CRUK, MRC, Breast Cancer Campaign (to SG).
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Lemarie, A., Grimm, S. Mitochondrial respiratory chain complexes: apoptosis sensors mutated in cancer?. Oncogene 30, 3985–4003 (2011). https://doi.org/10.1038/onc.2011.167
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DOI: https://doi.org/10.1038/onc.2011.167
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