13 June 2005
Mitochondrial complex II, or succinate dehydrogenase, is a key enzymatic complex involved in both the tricarboxylic acid (TCA) cycle and oxidative phosphorylation as part of the mitochondrial respiratory chain. Germline succinate dehydrogenase subunit A ( SDHA) mutations have been reported in a few patients with a classical mitochondrial neurodegenerative disease. Mutations in the genes encoding the three other succinate dehydrogenase subunits ( SDHB, SDHC and SDHD) have been identified in patients affected by familial or ‘apparently sporadic’ paraganglioma and/or pheochromocytoma, an autosomal inherited cancer-susceptibility syndrome. These discoveries have dramatically changed the work-up and genetic counseling of patients and families with paragangliomas and/or pheochromocytomas. The subsequent identification of germline mutations in the gene encoding fumarase – another TCA cycle enzyme – in a new hereditary form of susceptibility to renal, uterine and cutaneous tumors has highlighted the potential role of the TCA cycle and, more generally, of the mitochondria in cancer.