succinate dehydrogenase complex iron sulfur subunit B
Last updated 13 Jul 2021
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The SDHB gene provides instructions for making one of four subunits of the succinate dehydrogenase (SDH) enzyme. The SDH enzyme plays a critical role in mitochondria, which are structures inside cells that convert the energy from food into a form that cells can use.
Normal function
The SDHB gene provides instructions for making one of four subunits of the succinate dehydrogenase (SDH) enzyme. The SDH enzyme plays a critical role in mitochondria, which are structures inside cells that convert the energy from food into a form that cells can use.
Within mitochondria, the SDH enzyme links two important pathways in energy conversion: the citric acid cycle (or Krebs cycle) and oxidative phosphorylation. As part of the citric acid cycle, the SDH enzyme converts a compound called succinate to another compound called fumarate. Negatively charged particles called electrons are released during this reaction. The SDHB protein provides an attachment site for electrons as they are transferred to the oxidative phosphorylation pathway. In oxidative phosphorylation, the electrons help create an electrical charge that provides energy for the production of adenosine triphosphate (ATP), the cell's main energy source.
Succinate, the compound on which the SDH enzyme acts, is an oxygen sensor in the cell and can help turn on specific pathways that stimulate cells to grow in a low-oxygen environment (hypoxia). In particular, succinate stabilizes a protein called hypoxia-inducible factor (HIF) by preventing a reaction that would allow HIF to be broken down. HIF controls several important genes involved in cell division and the formation of new blood vessels in a hypoxic environment.
The SDHB gene is a tumour suppressor, which means it prevents cells from growing and dividing in an uncontrolled way.
Conditions referring to this gene or chromosome
Other names
DHSB_HUMAN
FLJ92337
IP
iron-sulfur subunit of complex II
PGL4
SDH
SDH1
SDH2
SDHIP
succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial
succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial precursor
succinate dehydrogenase complex subunit B, iron sulfur (Ip)
succinate dehydrogenase complex, subunit B, iron sulfur (Ip)
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Further reading and references
- succinate dehydrogenase complex iron sulfur subunit B; MedlinePlus, National Library of Medicine.
- Astuti D, Latif F, Dallol A, Dahia PL, Douglas F, George E, Skoldberg F, Husebye ES, Eng C, Maher ER. Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Am J Hum Genet. 2001 Jul;69(1):49-54. doi: 10.1086/321282. Epub 2001 Jun 12.
- Belinsky MG, Rink L, von Mehren M. Succinate dehydrogenase deficiency in pediatric and adult gastrointestinal stromal tumors. Front Oncol. 2013 May 17;3:117. doi: 10.3389/fonc.2013.00117. eCollection 2013.
- Burnichon N, Rohmer V, Amar L, Herman P, Leboulleux S, Darrouzet V, Niccoli P, Gaillard D, Chabrier G, Chabolle F, Coupier I, Thieblot P, Lecomte P, Bertherat J, Wion-Barbot N, Murat A, Venisse A, Plouin PF, Jeunemaitre X, Gimenez-Roqueplo AP; PGL.NET network. The succinate dehydrogenase genetic testing in a large prospective series of patients with paragangliomas. J Clin Endocrinol Metab. 2009 Aug;94(8):2817-27. doi: 10.1210/jc.2008-2504. Epub 2009 May 19.
- Gill AJ, Pachter NS, Clarkson A, Tucker KM, Winship IM, Benn DE, Robinson BG, Clifton-Bligh RJ. Renal tumors and hereditary pheochromocytoma-paraganglioma syndrome type 4. N Engl J Med. 2011 Mar 3;364(9):885-6. doi: 10.1056/NEJMc1012357. No abstract available.
- Gill AJ. Succinate dehydrogenase (SDH)-deficient neoplasia. Histopathology. 2018 Jan;72(1):106-116. doi: 10.1111/his.13277.
- Janeway KA, Kim SY, Lodish M, Nose V, Rustin P, Gaal J, Dahia PL, Liegl B, Ball ER, Raygada M, Lai AH, Kelly L, Hornick JL; NIH Pediatric and Wild-Type GIST Clinic; O'Sullivan M, de Krijger RR, Dinjens WN, Demetri GD, Antonescu CR, Fletcher JA, Helman L, Stratakis CA. Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):314-8. doi: 10.1073/pnas.1009199108. Epub 2010 Dec 20.
- Muller U. Pathological mechanisms and parent-of-origin effects in hereditary paraganglioma/pheochromocytoma (PGL/PCC). Neurogenetics. 2011 Aug;12(3):175-81. doi: 10.1007/s10048-011-0280-y. Epub 2011 Mar 9.
- Neumann HP, Bausch B, McWhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, Januszewicz A, Eng C, Smith WM, Munk R, Manz T, Glaesker S, Apel TW, Treier M, Reineke M, Walz MK, Hoang-Vu C, Brauckhoff M, Klein-Franke A, Klose P, Schmidt H, Maier-Woelfle M, Peczkowska M, Szmigielski C, Eng C; Freiburg-Warsaw-Columbus Pheochromocytoma Study Group. Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med. 2002 May 9;346(19):1459-66. doi: 10.1056/NEJMoa020152.
- Ni Y, He X, Chen J, Moline J, Mester J, Orloff MS, Ringel MD, Eng C. Germline SDHx variants modify breast and thyroid cancer risks in Cowden and Cowden-like syndrome via FAD/NAD-dependant destabilization of p53. Hum Mol Genet. 2012 Jan 15;21(2):300-10. doi: 10.1093/hmg/ddr459. Epub 2011 Oct 6.
- Ni Y, Zbuk KM, Sadler T, Patocs A, Lobo G, Edelman E, Platzer P, Orloff MS, Waite KA, Eng C. Germline mutations and variants in the succinate dehydrogenase genes in Cowden and Cowden-like syndromes. Am J Hum Genet. 2008 Aug;83(2):261-8. doi: 10.1016/j.ajhg.2008.07.011.
- Pasini B, McWhinney SR, Bei T, Matyakhina L, Stergiopoulos S, Muchow M, Boikos SA, Ferrando B, Pacak K, Assie G, Baudin E, Chompret A, Ellison JW, Briere JJ, Rustin P, Gimenez-Roqueplo AP, Eng C, Carney JA, Stratakis CA. Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD. Eur J Hum Genet. 2008 Jan;16(1):79-88. doi: 10.1038/sj.ejhg.5201904. Epub 2007 Aug 1.
- Pasini B, Stratakis CA. SDH mutations in tumorigenesis and inherited endocrine tumours: lesson from the phaeochromocytoma-paraganglioma syndromes. J Intern Med. 2009 Jul;266(1):19-42. doi: 10.1111/j.1365-2796.2009.02111.x.
- Pollard PJ, Briere JJ, Alam NA, Barwell J, Barclay E, Wortham NC, Hunt T, Mitchell M, Olpin S, Moat SJ, Hargreaves IP, Heales SJ, Chung YL, Griffiths JR, Dalgleish A, McGrath JA, Gleeson MJ, Hodgson SV, Poulsom R, Rustin P, Tomlinson IP. Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations. Hum Mol Genet. 2005 Aug 1;14(15):2231-9. doi: 10.1093/hmg/ddi227. Epub 2005 Jun 29.
- Ricketts C, Woodward ER, Killick P, Morris MR, Astuti D, Latif F, Maher ER. Germline SDHB mutations and familial renal cell carcinoma. J Natl Cancer Inst. 2008 Sep 3;100(17):1260-2. doi: 10.1093/jnci/djn254. Epub 2008 Aug 26.
- Selak MA, Armour SM, MacKenzie ED, Boulahbel H, Watson DG, Mansfield KD, Pan Y, Simon MC, Thompson CB, Gottlieb E. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell. 2005 Jan;7(1):77-85. doi: 10.1016/j.ccr.2004.11.022.
- Stratakis CA, Carney JA. The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney-Stratakis syndrome): molecular genetics and clinical implications. J Intern Med. 2009 Jul;266(1):43-52. doi: 10.1111/j.1365-2796.2009.02110.x.
- Vanharanta S, Buchta M, McWhinney SR, Virta SK, Peczkowska M, Morrison CD, Lehtonen R, Januszewicz A, Jarvinen H, Juhola M, Mecklin JP, Pukkala E, Herva R, Kiuru M, Nupponen NN, Aaltonen LA, Neumann HP, Eng C. Early-onset renal cell carcinoma as a novel extraparaganglial component of SDHB-associated heritable paraganglioma. Am J Hum Genet. 2004 Jan;74(1):153-9. doi: 10.1086/381054. Epub 2003 Dec 18.
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