Abstract
Mitochondrial defects have been associated with neurological disorders, as well as cancers. Two ubiquitously expressed mitochondrial enzymes--succinate dehydrogenase (SDH) and fumarate hydratase (FH, fumarase)--catalyse sequential steps in the Krebs tricarboxylic-acid cycle. Inherited heterozygous mutations in the genes encoding these enzymes cause predispositions to two types of inherited neoplasia syndromes that do not share any component tumours. Homozygous mutations in the same genes result in severe neurological impairment. Understanding this link between inherited cancer syndromes and neurological disease could provide further insights into the mechanisms by which mitochondrial deficiencies lead to tumour development.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Apoptosis / genetics
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Apoptosis / physiology
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Carcinoma, Renal Cell / enzymology
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Carcinoma, Renal Cell / genetics
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Citric Acid Cycle / genetics*
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Electron Transport Complex II
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Energy Metabolism
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Forecasting
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Free Radicals
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Fumarate Hydratase / deficiency
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Fumarate Hydratase / genetics
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Fumarate Hydratase / physiology*
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Heterozygote
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Homozygote
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Humans
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Kidney Neoplasms / enzymology
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Kidney Neoplasms / genetics
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Leiomyomatosis / enzymology
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Leiomyomatosis / genetics
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Mitochondria / enzymology*
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Mitochondrial Encephalomyopathies / enzymology*
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Mitochondrial Encephalomyopathies / genetics
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Multienzyme Complexes / deficiency
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Multienzyme Complexes / genetics
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Multienzyme Complexes / physiology*
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Mutation
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Neoplastic Syndromes, Hereditary / enzymology*
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Neoplastic Syndromes, Hereditary / genetics
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Neovascularization, Physiologic / genetics
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Neovascularization, Physiologic / physiology
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Oxidoreductases / deficiency
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Oxidoreductases / genetics
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Oxidoreductases / physiology*
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Paraganglioma / enzymology
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Paraganglioma / genetics
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Pheochromocytoma / enzymology
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Pheochromocytoma / genetics
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Protein Subunits
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Succinate Dehydrogenase / deficiency
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Succinate Dehydrogenase / genetics
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Succinate Dehydrogenase / physiology*
Substances
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Free Radicals
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Multienzyme Complexes
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Protein Subunits
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Oxidoreductases
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Electron Transport Complex II
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Succinate Dehydrogenase
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Fumarate Hydratase