Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial (CybS), also known as succinate dehydrogenase complex subunit D (SDHD), is a protein that in humans is encoded by the SDHD gene.[1][2][3]
SDHD, which stands for succinate dehydrogenase complex subunit D, is one of the two transmembrane subunits of the four-subunit succinate dehydrogenase protein complex that resides in the inner mitochondrial membrane. It also refers to the gene that codes for this protein. The other transmembrane subunit is SDHC. SDHD/SDHC are connected to the SDHB electron transfer subunit. SDHB in turn transfers electrons from the SDHA subunit to the SDHC/SDHD dimer.
Succinate dehydrogenase is an important enzyme in both the citric acid cycle and the electron transfer chain
The SDHD gene is located on chromosome 11, at locus 11q23. Names previously used for SDHD were PGL and PGL1.
[edit] Role in disease
Mutations in the SDHD gene can cause familial paraganglioma.
Germline mutations in SDHD were first linked to hereditary paraganglioma in 2000.[4] Since then, it has been shown that mutations in SDHB and to a lesser degree SDHC can cause paranglioma as well familial pheochromocytoma. Notably, the tumor spectrum is different for the different mutations. SDHB mutations often lead to metastatic disease that is extra-adrenal, while SDHD mutation related tumors are more typically benign, originating in the head and neck.
The exact mechanism for tumorigenesis is not determined, but it is suspected that malfunction of the SDH complex can cause a hypoxic response in the cell that leads to tumor formation. People living at higher altitudes (for example, the Andes mountains) are known to have an increased rate of benign paraganglioma, with the rate of disease increasing with the altitude of the population.
[edit] Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [5]
[edit] References
- ^ "Entrez Gene: succinate dehydrogenase complex". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6392.
- ^ Heutink P, van der Mey AG, Sandkuijl LA, van Gils AP, Bardoel A, Breedveld GJ, van Vliet M, van Ommen GJ, Cornelisse CJ, Oostra BA (April 1992). "A gene subject to genomic imprinting and responsible for hereditary paragangliomas maps to chromosome 11q23-qter". Hum. Mol. Genet. 1 (1): 7–10. doi:10.1093/hmg/1.1.7. PMID 1301144.
- ^ Hirawake H, Taniwaki M, Tamura A, Kojima S, Kita K (1997). "Cytochrome b in human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the components in liver mitochondria and chromosome assignment of the genes for the large (SDHC) and small (SDHD) subunits to 1q21 and 11q23". Cytogenet. Cell Genet. 79 (1-2): 132–8. doi:10.1159/000134700. PMID 9533030.
- ^ Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A, van der Mey A, Taschner PE, Rubinstein WS, Myers EN, Richard CW, Cornelisse CJ, Devilee P, Devlin B (February 2000). "Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma". Science 287 (5454): 848–51. doi:10.1126/science.287.5454.848. PMID 10657297.
- ^ The interactive pathway map can be edited at WikiPathways: "TCA_Cycle_WP78". http://www.wikipathways.org/index.php/Pathway:WP78.
[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.
- 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.
- Janecke AR, Willett-Brozick JE, Karas C, et al. (2010). "Identification of a 4.9-kilo base-pair Alu-mediated founder SDHD deletion in two extended paraganglioma families from Austria.". J. Hum. Genet. 55 (3): 182–5. doi:10.1038/jhg.2009.142. PMID 20111059.
- Cascón A, López-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.
- Waldmann J, Langer P, Habbe N, et al. (2009). "Mutations and polymorphisms in the SDHB, SDHD, VHL, and RET genes in sporadic and familial pheochromocytomas.". Endocrine 35 (3): 347–55. doi:10.1007/s12020-009-9178-y. PMID 19399650.
- Ricketts CJ, Forman JR, Rattenberry E, et al. (2010). "Tumor risks and genotype-phenotype-proteotype analysis in 358 patients with germline mutations in SDHB and SDHD.". Hum. Mutat. 31 (1): 41–51. doi:10.1002/humu.21136. PMID 19802898.
- 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.
- Martin TP, Irving RM, Maher ER (2007). "The genetics of paragangliomas: a review.". Clin Otolaryngol 32 (1): 7–11. doi:10.1111/j.1365-2273.2007.01378.x. PMID 17298303.
- 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.
- Talmud PJ, Drenos F, Shah S, et al. (2009). "Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.". Am. J. Hum. Genet. 85 (5): 628–42. doi:10.1016/j.ajhg.2009.10.014. PMC 2775832. PMID 19913121. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2775832.
- 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.
- Hensen EF, Jansen JC, Siemers MD, et al. (2010). "The Dutch founder mutation SDHD.D92Y shows a reduced penetrance for the development of paragangliomas in a large multigenerational family.". Eur. J. Hum. Genet. 18 (1): 62–6. doi:10.1038/ejhg.2009.112. PMC 2987152. PMID 19584903. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2987152.
- Brière 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.
- 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.
- Sevilla MA, Hermsen MA, Weiss MM, et al. (2009). "Chromosomal changes in sporadic and familial head and neck paragangliomas.". Otolaryngol Head Neck Surg 140 (5): 724–9. doi:10.1016/j.otohns.2009.01.004. PMID 19393419.
- Hendrickson SL, Lautenberger JA, Chinn LW, et al. (2010). "Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.". PLoS ONE 5 (9): e12862. doi:10.1371/journal.pone.0012862. PMC 2943476. PMID 20877624. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2943476.
- Erlic Z, Rybicki L, Peczkowska M, et al. (2009). "Clinical predictors and algorithm for the genetic diagnosis of pheochromocytoma patients.". Clin. Cancer Res. 15 (20): 6378–85. doi:10.1158/1078-0432.CCR-09-1237. PMID 19825962.
- Krawczyk A, Hasse-Lazar K, Pawlaczek A, et al. (2010). "Germinal mutations of RET, SDHB, SDHD, and VHL genes in patients with apparently sporadic pheochromocytomas and paragangliomas.". Endokrynol Pol 61 (1): 43–8. PMID 20205103.
- Bailey SD, Xie C, Do R, et al. (2010). "Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.". Diabetes Care 33 (10): 2250–3. doi:10.2337/dc10-0452. PMC 2945168. PMID 20628086. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2945168.
[edit] External links
|
PDB gallery
|
|
|
|
|
1zp0: Crystal Structure of Mitochondrial Respiratory Complex II bound with 3-nitropropionate and 2-thenoyltrifluoroacetone
|
|
|
|
1zoy: Crystal Structure of Mitochondrial Respiratory Complex II from porcine heart at 2.4 Angstroms
|
|
|
|
