title: Mitochondrial complex II and genomic imprinting in inheritance of paraganglioma tumors.
abstract: Germ line heterozygous mutations in the structural subunit genes of mitochondrial complex II (succinate dehydrogenase; SDH) and the regulatory gene SDHAF2 predispose to paraganglioma tumors which show constitutive activation of hypoxia inducible pathways. Mutations in SDHD and SDHAF2 cause highly penetrant multifocal tumor development after a paternal transmission, whereas maternal transmission rarely, if ever, leads to tumor development. This transmission pattern is consistent with genomic imprinting. Recent molecular evidence supports a model for tissue-specific imprinted regulation of the SDHD gene by a long range epigenetic mechanism. In addition, there is evidence of SDHB mRNA editing in peripheral blood mononuclear cells and long-term balancing selection operating on the SDHA gene. Regulation of SDH subunit expression by diverse epigenetic mechanisms implicates a crucial dosage-dependent role for SDH in oxygen homeostasis. This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease.
authors.affiliation: Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY, USA. bora.baysal@roswellpark.org
authors.forename: Bora E
authors.initials: BE
authors.lastname: Baysal
mesh_terms: D042963:Electron Transport Complex II / Q000235:genetics* / Q000378:metabolism; D018392:Genomic Imprinting; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D009154:Mutation; D010235:Paraganglioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013385:Succinate Dehydrogenase / Q000235:genetics / Q000378:metabolism
chemical_list: C491545:SDHD protein, human; C478189:respiratory complex II; D042963:Electron Transport Complex II; C511268:SDHA protein, human; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase