Role of mitochondrial mutations in cancer
A role for mitochondria in cancer causation has been implicated through identification of mutations in the mitochondrial DNA (mtDNA) and in nuclear-encoded mitochondrial genes. Although many mtDNA mutations were detected in common tumors, an unequivocal causal link between heritable mitochondrial abnormalities and cancer is provided only by the germ line mutations in the nuclear-encoded genes for succinate dehydrogenase (mitochondrial complex II) and fumarate hydratase (fumarase). The absence of evidence for highly penetrant tumors caused by inherited mtDNA mutations contrasts with the frequent occurrence of mtDNA mutations in many different tumor types. Thus, either the majority of diverse mtDNA mutations observed in tumors are not important for the process of carcinogenesis or that they play a common oncogenic role.
Key WordsParaganglioma hereditary leiomyomatosis and renal cell cancer syndrome Krebs cycle oxidative phosphorylation pheochromocytoma electron transport chain
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- 28.Shoffner JM. Oxidative phosphorylation diseases. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular basis of inherited disease. New York, NY: McGraw-Hill, 2001; 2367–2423.Google Scholar
- 38.Piruat JI, Pintado CO, Ortega-Saenz P, Roche M, Lopez-Barneo J. The mitochondrial SDHD gene is required for early embryogenesis, and its partial deficiency results in persistent carotid body glomus cell activation with full responsiveness to hypoxia. Mol Cell Biol 24:10933–10940, 2004.PubMedCrossRefGoogle Scholar