کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1942251 | 1052598 | 2013 | 5 صفحه PDF | دانلود رایگان |

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.
► Parent-of-origin effects in inheritance of paraganglioma tumors are discussed.
► A long range epigenetic mechanism may account for genomic imprinting of SDHD.
► Diverse regulatory mechanisms of complex II suggest a crucial role in oxygen homeostasis.
Journal: Biochimica et Biophysica Acta (BBA) - Bioenergetics - Volume 1827, Issue 5, May 2013, Pages 573–577