Succinate dehydrogenase complex subunit C

Succinate dehydrogenase complex, subunit C, integral membrane protein, 15kDa
PDB rendering based on 1zp0.
Available structures PDB 1zoy, 1zp0
Identifiers
Symbols	SDHC; CYB560; CYBL; PGL3; QPS1; SDH3
External IDs	OMIM: 602413 MGI: 1913302 HomoloGene: 2256 GeneCards: SDHC Gene
Gene Ontology Molecular function • succinate dehydrogenase activity • electron carrier activity • heme binding • metal ion binding Cellular component • mitochondrion • mitochondrial inner membrane • mitochondrial inner membrane • mitochondrial respiratory chain complex II • membrane • integral to membrane • respiratory chain complex II • plasma membrane succinate dehydrogenase complex Biological process • tricarboxylic acid cycle • transport • aerobic respiration • respiratory electron transport chain • oxidation-reduction process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6391	66052
Ensembl	ENSG00000143252	ENSMUSG00000058076
UniProt	Q99643	Q9CZB0
RefSeq (mRNA)	NM_001035511.1	NM_025321.3
RefSeq (protein)	NP_001030588.1	NP_079597.2
Location (UCSC)	Chr 1: 161.28 – 161.33 Mb	Chr 1: 173.06 – 173.08 Mb
PubMed search	[1]	[2]

Succinate dehydrogenase complex subunit C, also known as succinate dehydrogenase cytochrome b560 subunit, mitochondrial, is a protein that in humans is encoded by the SDHC gene.

Gene

The gene that codes for the SDHC protein is nuclear, even though the protein is located in the inner membrane of the mitochondria. The location of the gene in humans is on the first chromosome at q21. The gene is partitioned in 6 exons. The expressed protein has 170 amino acids.

Function

The SDHC protein one of four nuclear-encoded subunits that comprise succinate dehydrogenase, also known as the mitochondrial complex II, a key enzyme complex of the citric acid cycle and aerobic respiratory chains of mitochondria. The encoded protein is one of two integral membrane proteins that anchor other subunits of the complex, which form the catalytic core, to the inner mitochondrial membrane.

The succinate dehydrogenase (SDH) protein complex catalyzes the oxidation of succinate (succinate + ubiquinone => fumarate + ubiquinol). The SDHA subunit is connected to the SDHB subunit on the hydrophilic, catalytic end of the complex. Electrons removed from succinate transfer SDHA to SDHB and further to the SDHC/SDHD subunits on the hydrophobic end of the complex anchored in the mitochondrial membrane.

The SDH complex is located on the inner membrane of the mitochondria and participates in both the Citric Acid Cycle and Respiratory chain.

SDHC acts as an intermediate in the basic SDH enzyme action:

1. SDHA converts succinate to fumarate as part of the Citric Acid Cycle. This reaction also converts FAD to FADH₂.
2. Electrons from the FADH₂ are transferred to the SDHB subunit iron clusters [2Fe-2S],[4Fe-4S],[3Fe-4S]. This function is part of the Respiratory chain
3. Finally the electrons are transferred to the Ubiquinone (Q) pool via the SDHC/SDHD subunits.

Clinical significance

Mutations in this gene have been associated with paragangliomas.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.

[[File:

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

|{{{bSize}}}px]]

Citric_acid_cycle edit

Further reading

• Bayley JP, Weiss MM, Grimbergen A, et al. (2009). "Molecular characterization of novel germline deletions affecting SDHD and SDHC in pheochromocytoma and paraganglioma patients.". Endocr. Relat. Cancer 16 (3): 929–37. doi:10.1677/ERC-09-0084. PMID 19546167. 
• Pasini B, McWhinney SR, Bei T, et al. (2008). "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. 16 (1): 79–88. doi:10.1038/sj.ejhg.5201904. PMID 17667967. 
• Gaal J, Burnichon N, Korpershoek E, et al. (2010). "Isocitrate dehydrogenase mutations are rare in pheochromocytomas and paragangliomas.". J. Clin. Endocrinol. Metab. 95 (3): 1274–8. doi:10.1210/jc.2009-2170. PMID 19915015. 
• Milosevic D, Lundquist P, Cradic K, et al. (2010). "Development and validation of a comprehensive mutation and deletion detection assay for SDHB, SDHC, and SDHD.". Clin. Biochem. 43 (7-8): 700–4. doi:10.1016/j.clinbiochem.2010.01.016. PMID 20153743. 
• Bonache S, Martí­nez J, Fernández M, et al. (2007). "Single nucleotide polymorphisms in succinate dehydrogenase subunits and citrate synthase genes: association results for impaired spermatogenesis.". Int. J. Androl. 30 (3): 144–52. doi:10.1111/j.1365-2605.2006.00730.x. PMID 17298551. 
• Cascán A, Lápez-Jiménez E, Landa I, et al. (2009). "Rationalization of genetic testing in patients with apparently sporadic pheochromocytoma/paraganglioma.". Horm. Metab. Res. 41 (9): 672–5. doi:10.1055/s-0029-1202814. PMID 19343621. 
• Goto Y, Ando T, Naito M, et al.. "No association of an SDHC gene polymorphism with gastric cancer.". Asian Pac. J. Cancer Prev. 7 (4): 525–8. PMID 17250422. 
• Cascán A, Pita G, Burnichon N, et al. (2009). "Genetics of pheochromocytoma and paraganglioma in Spanish patients.". J. Clin. Endocrinol. Metab. 94 (5): 1701–5. doi:10.1210/jc.2008-2756. PMID 19258401. 
• Boedeker CC, Neumann HP, Maier W, et al. (2007). "Malignant head and neck paragangliomas in SDHB mutation carriers.". Otolaryngol Head Neck Surg 137 (1): 126–9. doi:10.1016/j.otohns.2007.01.015. PMID 17599579. 
• Gill AJ, Benn DE, Chou A, et al. (2010). "Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes.". Hum. Pathol. 41 (6): 805–14. doi:10.1016/j.humpath.2009.12.005. PMID 20236688. 
• Ricketts C, Woodward ER, Killick P, et al. (2008). "Germline SDHB mutations and familial renal cell carcinoma.". J. Natl. Cancer Inst. 100 (17): 1260–2. doi:10.1093/jnci/djn254. PMID 18728283. 
• McWhinney SR, Pasini B, Stratakis CA, (2007). "Familial gastrointestinal stromal tumors and germ-line mutations.". N. Engl. J. Med. 357 (10): 1054–6. doi:10.1056/NEJMc071191. PMID 17804857. 
• Eng C, Kiuru M, Fernandez MJ, Aaltonen LA (2003). "A role for mitochondrial enzymes in inherited neoplasia and beyond.". Nat. Rev. Cancer 3 (3): 193–202. doi:10.1038/nrc1013. PMID 12612654. 
• Hermsen MA, Sevilla MA, Llorente JL, et al. (2010). "Relevance of germline mutation screening in both familial and sporadic head and neck paraganglioma for early diagnosis and clinical management.". Cell. Oncol. 32 (4): 275–83. doi:10.3233/CLO-2009-0498. PMID 20208144. 
• Brií¨re JJ, Favier J, El Ghouzzi V, et al. (2005). "Succinate dehydrogenase deficiency in human.". Cell. Mol. Life Sci. 62 (19-20): 2317–24. doi:10.1007/s00018-005-5237-6. PMID 16143825. 
• Mannelli M, Castellano M, Schiavi F, et al. (2009). "Clinically guided genetic screening in a large cohort of italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas.". J. Clin. Endocrinol. Metab. 94 (5): 1541–7. doi:10.1210/jc.2008-2419. PMID 19223516. 
• Richalet JP, Gimenez-Roqueplo AP, Peyrard S, et al. (2009). "A role for succinate dehydrogenase genes in low chemoresponsiveness to hypoxia?". Clin. Auton. Res. 19 (6): 335–42. doi:10.1007/s10286-009-0028-z. PMID 19768395. 
• Pigny P, Cardot-Bauters C, Do Cao C, et al. (2009). "Should genetic testing be performed in each patient with sporadic pheochromocytoma at presentation?". Eur. J. Endocrinol. 160 (2): 227–31. doi:10.1530/EJE-08-0574. PMID 19029228. 
• Korpershoek E, Van Nederveen FH, Dannenberg H, et al. (2006). "Genetic analyses of apparently sporadic pheochromocytomas: the Rotterdam experience.". Ann. N. Y. Acad. Sci. 1073: 138–48. doi:10.1196/annals.1353.014. PMID 17102080. 
• Wang L, McDonnell SK, Hebbring SJ, et al. (2008). "Polymorphisms in mitochondrial genes and prostate cancer risk.". Cancer Epidemiol. Biomarkers Prev. 17 (12): 3558–66. doi:10.1158/1055-9965.EPI-08-0434. PMC 2750891. PMID 19064571. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2750891. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.