Succinate Dehydrogenase Loss in Familial Paraganglioma: Biochemistry, Genetics, and Epigenetics

<div>Potential <i>α</i>-KG-dependent dioxygenase targets susceptible to succinate inhibition. In SDH-deficient cells, succinate accumulates in mitochondria and diffuses into the cytosol and nucleus. Succinate inhibits <i>α</i>-KG-dependent dioxygenases resulting in accumulation of (A) HIF1<i>α</i> and HIF2<i>α</i>, (B) hypermethylation of histones, (C) hypermethylation of deoxycytidine, (D) accumulation of immature collagen, (E) accumulation of N<sup><i>ε</i></sup>-trimethyllysine, (F) damaged DNA, and (G) accumulation of N6-methyladenosine on mRNA.</div>

International Journal of Endocrinology

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Figure 4: Succinate Dehydrogenase Loss in Familial Paraganglioma: Biochemistry, Genetics, and Epigenetics 