Mitochondrial complex II and genomic imprinting in inheritance of paraganglioma tumors

Biochim Biophys Acta. 2013 May;1827(5):573-7. doi: 10.1016/j.bbabio.2012.12.005. Epub 2013 Jan 2.


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.

Publication types

  • Review

MeSH terms

  • Electron Transport Complex II / genetics*
  • Electron Transport Complex II / metabolism
  • Genomic Imprinting*
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Models, Genetic
  • Mutation*
  • Paraganglioma / genetics*
  • Paraganglioma / metabolism
  • Paraganglioma / pathology
  • Succinate Dehydrogenase / genetics
  • Succinate Dehydrogenase / metabolism


  • SDHD protein, human
  • respiratory complex II
  • Electron Transport Complex II
  • SDHA protein, human
  • SDHB protein, human
  • Succinate Dehydrogenase