# SDHA

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Protein-coding gene in humans

SDHA Identifiers Aliases SDHA, CMD1GG, FP, PGL5, SDH1, SDH2, SDHF, succinate dehydrogenase complex flavoprotein subunit A, MC2DN1, NDAXOA External IDs OMIM: 600857; MGI: 1914195; HomoloGene: 3073; GeneCards: SDHA; OMA:SDHA - orthologs Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5p15.33 Start 218,303 bp[1] End 257,082 bp[1] Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13|13 C1 Start 74,470,373 bp[2] End 74,498,399 bp[2] RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in apex of heart left ventricle mucosa of transverse colon right auricle of heart skeletal muscle tissue muscle of thigh duodenum gastrocnemius muscle right lobe of liver right adrenal cortex Top expressed in right ventricle sternocleidomastoid muscle digastric muscle temporal muscle right kidney vastus lateralis muscle triceps brachii muscle aortic valve medial head of gastrocnemius muscle supraoptic nucleus More reference expression data BioGPS n/a Gene ontology Molecular function oxidoreductase activity oxidoreductase activity, acting on the CH-CH group of donors succinate dehydrogenase activity protein binding succinate dehydrogenase (ubiquinone) activity flavin adenine dinucleotide binding electron transfer activity Cellular component mitochondrial inner membrane myelin sheath mitochondrial respiratory chain complex II, succinate dehydrogenase complex (ubiquinone) membrane mitochondrion nucleolus plasma membrane succinate dehydrogenase complex Biological process succinate metabolic process tricarboxylic acid cycle nervous system development electron transport chain respiratory electron transport chain mitochondrial electron transport, succinate to ubiquinone anaerobic respiration Sources:Amigo / QuickGO Orthologs Species Human Mouse Entrez 6389 66945 Ensembl ENSG00000073578 ENSMUSG00000021577 UniProt P31040 Q8K2B3 RefSeq (mRNA) NM_001294332 NM_004168 NM_001330758 NM_023281 RefSeq (protein) NP_001281261 NP_001317687 NP_004159 NP_075770 Location (UCSC) Chr 5: 0.22 – 0.26 Mb Chr 13: 74.47 – 74.5 Mb PubMed search [3] [4] Wikidata View/Edit Human View/Edit Mouse

**Succinate dehydrogenase complex, subunit A, flavoprotein variant** is a [protein](/source/Protein) that in humans is encoded by the *SDHA* [gene](/source/Gene).[5] This gene encodes a major catalytic subunit of [succinate-ubiquinone oxidoreductase](/source/Succinate_dehydrogenase), a complex of the mitochondrial respiratory chain. The complex is composed of four nuclear-encoded subunits and is localized in the mitochondrial inner membrane. SDHA contains the [FAD](/source/Flavin_adenine_dinucleotide) binding site where [succinate](/source/Succinate) is deprotonated and converted to [fumarate](/source/Fumarate). Mutations in this gene have been associated with a form of mitochondrial respiratory chain deficiency known as Leigh Syndrome. A [pseudogene](/source/Pseudogene) has been identified on chromosome 3q29. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[6]

## Structure

The *SDHA* gene is located on the p arm of [chromosome 5](/source/Chromosome_5) at locus 15 and is composed of 17 exons.[6] The SDHA [protein](/source/Protein) encoded by this gene is 664 amino acids long and weighs 72.7 kDA.[7][8]

SDHA protein has four subdomains, including capping domain, helical domain, [C-terminal](/source/C-terminus) domain and most notably, [β-barrel](/source/Beta_barrel) FAD-binding domain at [N-terminus](/source/N-terminus). Therefore, SDHA is a [flavoprotein](/source/Flavoprotein) (Fp) due to the [prosthetic group](/source/Cofactor_(biochemistry)) [flavin adenine dinucleotide](/source/Flavin_adenine_dinucleotide) (FAD). Crystal structure suggests that FAD is covalently bound to a [histidine](/source/Histidine) residue (His99) and further coordinated by [hydrogen bonds](/source/Hydrogen_bond) with number of other amino acid residues within the FAD-binding domain. FAD which is derived from [riboflavin](/source/Riboflavin) (vitamin B2) is thus essential cofactor for SDHA and whole complex II function.[9]

## Function

The SDH complex is located on the inner membrane of the [mitochondria](/source/Mitochondria) and participates in both the [citric acid cycle](/source/Citric_acid_cycle) and the [respiratory chain](/source/Respiratory_chain). The [succinate dehydrogenase](/source/Succinate_dehydrogenase) (SDH) protein complex catalyzes the oxidation of succinate (succinate + ubiquinone => fumarate + ubiquinol). Electrons removed from succinate transfer to SDHA, transfer across [SDHB](/source/SDHB) through [iron sulphur clusters](/source/Iron_sulfur_cluster) to the [SDHC](/source/Succinate_dehydrogenase_complex_subunit_C)/[SDHD](/source/SDHD) subunits on the hydrophobic end of the complex anchored in the mitochondrial membrane.

Initially, SDHA oxidizes [succinate](/source/Succinate) via [deprotonation](/source/Deprotonation) at the [FAD](/source/Flavin_adenine_dinucleotide) binding site, forming [FADH2](/source/FADH2) and leaving [fumarate](/source/Fumarate), loosely bound to the active site, free to exit the protein. The electrons derived from succinate tunnel along the [Fe-S] relay in the [SDHB](/source/SDHB) subunit until they reach the [3Fe-4S] [iron sulfur cluster](/source/Iron_sulfur_cluster). The electrons are then transferred to an awaiting [ubiquinone](/source/Ubiquinone) molecule at the Q pool active site in the SDHC/SDHD dimer. The O1 [carbonyl](/source/Carbonyl) oxygen of ubiquinone is oriented at the active site by [hydrogen bond](/source/Hydrogen_bond) interactions with Tyr83 of [SDHD](/source/SDHD). The presence of electrons in the [3Fe-4S] iron sulphur cluster induces the movement of ubiquinone into a second orientation. This facilitates a second hydrogen bond interaction between the O4 carbonyl group of ubiquinone and Ser27 of [SDHC](/source/SDHC_(gene)). Following the first single electron reduction step, a [semiquinone](/source/Semiquinone) radical species is formed. The second electron arrives from the [3Fe-4S] cluster to provide full reduction of the ubiquinone to [ubiquinol](/source/Ubiquinol).[10]

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

1. **SDHA converts [succinate](/source/Succinate) to [fumarate](/source/Fumarate) as part of the [citric acid cycle](/source/Citric_acid_cycle)**. This reaction also converts FAD to FADH2.

1. 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](/source/Respiratory_chain)

1. Finally the electrons are transferred to the [Ubiquinone](/source/Ubiquinone) (Q) pool via the [SDHC](/source/Succinate_dehydrogenase_complex_subunit_C)/[SDHD](/source/SDHD) subunits.

## Clinical significance

Because of the complexity of SDHA's locus, SDHA was rarely analyzed,[11] but in an increasing amount of research, it's been found that mutations in SDHA are pathogenic for a number of conditions, including hereditary pheochromocytoma-paraganglioma (PPGL) syndrome, mitochondrial complex II deficiency, gastrointestinal stromal tumors, Leigh syndrome, dilated cardiomyopathy, and possible relation with pituitary adenomas, adrenal carcinomas, and other neuroendocrine tumors.[12] Hereditary PPGL syndrome associated with mutations in SDHA is called "Paragangliomas 5" with likely lower penetrance than other SDHx mutations.[13]

[Bi-allelic](/source/Allele) mutations in SDHA are known to be pathogenic for infant or early childhood [Leigh syndrome](/source/Leigh_syndrome), a progressive brain disorder.[14][15][16] It is not known, however, how mutations in the SDHA gene are related to the specific features of Leigh syndrome. There is some link between Leigh syndrome as a phenotype of mitochondrial complex II deficiency, but both can occur without the other as relating to SDHA mutations.[17]

SDHA is a tumour suppressor gene, and heterozygous carriers have an increased risk of [paragangliomas](/source/Paraganglioma) as well as [pheochromocytomas](/source/Pheochromocytoma) and renal cancer.[18] Risk management for heterozygous carriers of an SDHA mutation typically involve monitoring via annual urine tests for metanephrines and catecholamines as well as non-radiation imaging such as MRIs. PET scans and radiation imaging are used but should be limited to prevent radiation exposure.[19]

## Interactive pathway map

*Click on genes, proteins and metabolites below to link to respective articles.* [§ 1]

[[File:

]]

TCACycle_WP78  [edit](http://www.wikipathways.org/index.php/Pathway:WP78)

1. **[^](#cite_ref-WikiPathways_20-0)** The interactive pathway map can be edited at WikiPathways: ["TCACycle_WP78"](http://www.wikipathways.org/index.php/Pathway:WP78).

## References

1. ^ [***a***](#cite_ref-refGRCh38Ensembl_1-0) [***b***](#cite_ref-refGRCh38Ensembl_1-1) [***c***](#cite_ref-refGRCh38Ensembl_1-2) [GRCh38: Ensembl release 89: ENSG00000073578](http://May2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000073578) – [Ensembl](/source/Ensembl_genome_database_project), May 2017

1. ^ [***a***](#cite_ref-refGRCm38Ensembl_2-0) [***b***](#cite_ref-refGRCm38Ensembl_2-1) [***c***](#cite_ref-refGRCm38Ensembl_2-2) [GRCm38: Ensembl release 89: ENSMUSG00000021577](http://May2017.archive.ensembl.org/Mus_musculus/Gene/Summary?db=core;g=ENSMUSG00000021577) – [Ensembl](/source/Ensembl_genome_database_project), May 2017

1. **[^](#cite_ref-3)** ["Human PubMed Reference:"](https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=6389). *National Center for Biotechnology Information, U.S. National Library of Medicine*.

1. **[^](#cite_ref-4)** ["Mouse PubMed Reference:"](https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=66945). *National Center for Biotechnology Information, U.S. National Library of Medicine*.

1. **[^](#cite_ref-pmid7798181_5-0)** Hirawake H, Wang H, Kuramochi T, Kojima S, Kita K (July 1994). ["Human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the flavoprotein (Fp) subunit of liver mitochondria"](https://doi.org/10.1093%2Foxfordjournals.jbchem.a124497). *Journal of Biochemistry*. **116** (1): 221–7. [doi](/source/Doi_(identifier)):[10.1093/oxfordjournals.jbchem.a124497](https://doi.org/10.1093%2Foxfordjournals.jbchem.a124497). [PMID](/source/PMID_(identifier)) [7798181](https://pubmed.ncbi.nlm.nih.gov/7798181).

1. ^ [***a***](#cite_ref-entrez_6-0) [***b***](#cite_ref-entrez_6-1) ["Entrez Gene: succinate dehydrogenase complex"](https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=6389).

1. **[^](#cite_ref-COPaKB_7-0)** Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, et al. (October 2013). ["Integration of cardiac proteome biology and medicine by a specialized knowledgebase"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076475). *Circulation Research*. **113** (9): 1043–53. [doi](/source/Doi_(identifier)):[10.1161/CIRCRESAHA.113.301151](https://doi.org/10.1161%2FCIRCRESAHA.113.301151). [PMC](/source/PMC_(identifier)) [4076475](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076475). [PMID](/source/PMID_(identifier)) [23965338](https://pubmed.ncbi.nlm.nih.gov/23965338).

1. **[^](#cite_ref-url_COPaKB_8-0)** ["SDHA - Succinate dehydrogenase \[ubiquinone\] flavoprotein subunit, mitochondrial"](https://web.archive.org/web/20180719161721/https://amino.heartproteome.org/web/protein/P31040). *Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)*. Archived from [the original](https://amino.heartproteome.org/web/protein/P31040) on 2018-07-19. Retrieved 2018-07-18.

1. **[^](#cite_ref-9)** Van Vranken JG, Na U, Winge DR, Rutter J (March–April 2015). ["Protein-mediated assembly of succinate dehydrogenase and its cofactors"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653115). *Critical Reviews in Biochemistry and Molecular Biology*. **50** (2): 168–80. [doi](/source/Doi_(identifier)):[10.3109/10409238.2014.990556](https://doi.org/10.3109%2F10409238.2014.990556). [PMC](/source/PMC_(identifier)) [4653115](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653115). [PMID](/source/PMID_(identifier)) [25488574](https://pubmed.ncbi.nlm.nih.gov/25488574).

1. **[^](#cite_ref-10)** Horsefield R, Yankovskaya V, Sexton G, Whittingham W, Shiomi K, Omura S, et al. (March 2006). ["Structural and computational analysis of the quinone-binding site of complex II (succinate-ubiquinone oxidoreductase): a mechanism of electron transfer and proton conduction during ubiquinone reduction"](https://doi.org/10.1074%2Fjbc.m508173200). *The Journal of Biological Chemistry*. **281** (11): 7309–16. [doi](/source/Doi_(identifier)):[10.1074/jbc.m508173200](https://doi.org/10.1074%2Fjbc.m508173200). [PMID](/source/PMID_(identifier)) [16407191](https://pubmed.ncbi.nlm.nih.gov/16407191).

1. **[^](#cite_ref-11)** Wagner AJ, Remillard SP, Zhang YX, Doyle LA, George S, Hornick JL (February 2013). ["Loss of expression of SDHA predicts SDHA mutations in gastrointestinal stromal tumors"](https://doi.org/10.1038%2Fmodpathol.2012.153). *Mod Pathol*. **26** (2): 289–94. [doi](/source/Doi_(identifier)):[10.1038/modpathol.2012.153](https://doi.org/10.1038%2Fmodpathol.2012.153). [PMID](/source/PMID_(identifier)) [22955521](https://pubmed.ncbi.nlm.nih.gov/22955521).

1. **[^](#cite_ref-12)** ["SDHA\[gene\] ▶ GRCh37"](https://www.ncbi.nlm.nih.gov/clinvar/?term=SDHA%5Bgene%5D&redir=gene). *ClinVar*. National Library of Medicine.

1. **[^](#cite_ref-13)** van der Tuin K, Mensenkamp AR, Tops CM, Corssmit EP, Dinjens WN, van de Horst-Schrivers AN, Jansen JC, de Jong MM, Kunst HP, Kusters B, Leter EM, Morreau H, van Nesselrooij BM, Oldenburg RA, Spruijt L, Hes FJ, Timmers HJ (February 2018). "Clinical Aspects of SDHA-Related Pheochromocytoma and Paraganglioma: A Nationwide Study". *J Clin Endocrinol Metab*. **103** (2): 438–445. [doi](/source/Doi_(identifier)):[10.1210/jc.2017-01762](https://doi.org/10.1210%2Fjc.2017-01762). [PMID](/source/PMID_(identifier)) [29177515](https://pubmed.ncbi.nlm.nih.gov/29177515). "CORRIGENDUM FOR "Clinical Aspects of SDHA-Related Pheochromocytoma and Paraganglioma: A Nationwide Study"". *J Clin Endocrinol Metab*. **103** (5): 2077. May 2018. [doi](/source/Doi_(identifier)):[10.1210/jc.2018-00533](https://doi.org/10.1210%2Fjc.2018-00533). [hdl](/source/Hdl_(identifier)):[1887/79414](https://hdl.handle.net/1887%2F79414). [PMID](/source/PMID_(identifier)) [29538659](https://pubmed.ncbi.nlm.nih.gov/29538659).

1. **[^](#cite_ref-14)** ["Leigh syndrome"](https://medlineplus.gov/genetics/condition/leigh-syndrome/). *Genetics Home Reference*. U.S. National Library of Medicine. Retrieved 30 July 2018.

1. **[^](#cite_ref-15)** Pagnamenta AT, Hargreaves IP, Duncan AJ, Taanman JW, Heales SJ, Land JM, et al. (November 2006). "Phenotypic variability of mitochondrial disease caused by a nuclear mutation in complex II". *Molecular Genetics and Metabolism*. **89** (3): 214–21. [doi](/source/Doi_(identifier)):[10.1016/j.ymgme.2006.05.003](https://doi.org/10.1016%2Fj.ymgme.2006.05.003). [PMID](/source/PMID_(identifier)) [16798039](https://pubmed.ncbi.nlm.nih.gov/16798039).

1. **[^](#cite_ref-16)** Van Coster R, Seneca S, Smet J, Van Hecke R, Gerlo E, Devreese B, et al. (July 2003). "Homozygous Gly555Glu mutation in the nuclear-encoded 70 kDa flavoprotein gene causes instability of the respiratory chain complex II". *American Journal of Medical Genetics. Part A*. **120A** (1): 13–8. [doi](/source/Doi_(identifier)):[10.1002/ajmg.a.10202](https://doi.org/10.1002%2Fajmg.a.10202). [PMID](/source/PMID_(identifier)) [12794685](https://pubmed.ncbi.nlm.nih.gov/12794685). [S2CID](/source/S2CID_(identifier)) [30987591](https://api.semanticscholar.org/CorpusID:30987591).

1. **[^](#cite_ref-17)** Fullerton M, McFarland R, Taylor RW, Alston CL (2020). ["The genetic basis of isolated mitochondrial complex II deficiency"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758838). *Mol Genet Metab*. **131** (1–2): 53–65. [doi](/source/Doi_(identifier)):[10.1016/j.ymgme.2020.09.009](https://doi.org/10.1016%2Fj.ymgme.2020.09.009). [PMC](/source/PMC_(identifier)) [7758838](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758838). [PMID](/source/PMID_(identifier)) [33162331](https://pubmed.ncbi.nlm.nih.gov/33162331).

1. **[^](#cite_ref-18)** Reference, Genetics Home. ["SDHA"](https://medlineplus.gov/genetics/gene/sdha/). *Genetics Home Reference*. Retrieved 2016-08-31.

1. **[^](#cite_ref-19)** ["SDHA, SDHB or SDHC-related familial paraganglioma-phaeochromocytoma – risk management"](https://www.eviq.org.au/cancer-genetics/adult/risk-management/4066-sdhd-or-sdhaf2-related-familial-paraganglioma). *eviQ Cancer Treatments Online*. Cancer Institute NSW. 22 February 2022. 4066 v.3.

## Further reading

- Aboulaich N, Vainonen JP, Strålfors P, Vener AV (October 2004). ["Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1134064). *The Biochemical Journal*. **383** (Pt 2): 237–48. [doi](/source/Doi_(identifier)):[10.1042/BJ20040647](https://doi.org/10.1042%2FBJ20040647). [PMC](/source/PMC_(identifier)) [1134064](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1134064). [PMID](/source/PMID_(identifier)) [15242332](https://pubmed.ncbi.nlm.nih.gov/15242332).

- Bonache S, Martínez J, Fernández M, Bassas L, Larriba S (June 2007). ["Single nucleotide polymorphisms in succinate dehydrogenase subunits and citrate synthase genes: association results for impaired spermatogenesis"](https://doi.org/10.1111%2Fj.1365-2605.2006.00730.x). *International Journal of Andrology*. **30** (3): 144–52. [doi](/source/Doi_(identifier)):[10.1111/j.1365-2605.2006.00730.x](https://doi.org/10.1111%2Fj.1365-2605.2006.00730.x). [PMID](/source/PMID_(identifier)) [17298551](https://pubmed.ncbi.nlm.nih.gov/17298551).

- Horváth R, Abicht A, Holinski-Feder E, Laner A, Gempel K, Prokisch H, et al. (January 2006). ["Leigh syndrome caused by mutations in the flavoprotein (Fp) subunit of succinate dehydrogenase (SDHA)"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2117401). *Journal of Neurology, Neurosurgery, and Psychiatry*. **77** (1): 74–6. [doi](/source/Doi_(identifier)):[10.1136/jnnp.2005.067041](https://doi.org/10.1136%2Fjnnp.2005.067041). [PMC](/source/PMC_(identifier)) [2117401](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2117401). [PMID](/source/PMID_(identifier)) [16361598](https://pubmed.ncbi.nlm.nih.gov/16361598).

- Kullberg M, Nilsson MA, Arnason U, Harley EH, Janke A (August 2006). ["Housekeeping genes for phylogenetic analysis of eutherian relationships"](https://doi.org/10.1093%2Fmolbev%2Fmsl027). *Molecular Biology and Evolution*. **23** (8): 1493–503. [doi](/source/Doi_(identifier)):[10.1093/molbev/msl027](https://doi.org/10.1093%2Fmolbev%2Fmsl027). [PMID](/source/PMID_(identifier)) [16751257](https://pubmed.ncbi.nlm.nih.gov/16751257).

- Tomitsuka E, Kita K, Esumi H (2009). ["Regulation of succinate-ubiquinone reductase and fumarate reductase activities in human complex II by phosphorylation of its flavoprotein subunit"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561849). *Proceedings of the Japan Academy. Series B, Physical and Biological Sciences*. **85** (7): 258–65. [Bibcode](/source/Bibcode_(identifier)):[2009PJAB...85..258T](https://ui.adsabs.harvard.edu/abs/2009PJAB...85..258T). [doi](/source/Doi_(identifier)):[10.2183/pjab.85.258](https://doi.org/10.2183%2Fpjab.85.258). [PMC](/source/PMC_(identifier)) [3561849](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561849). [PMID](/source/PMID_(identifier)) [19644226](https://pubmed.ncbi.nlm.nih.gov/19644226).

- Hao HX, Khalimonchuk O, Schraders M, Dephoure N, Bayley JP, Kunst H, et al. (August 2009). ["SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881419). *Science*. **325** (5944): 1139–42. [Bibcode](/source/Bibcode_(identifier)):[2009Sci...325.1139H](https://ui.adsabs.harvard.edu/abs/2009Sci...325.1139H). [doi](/source/Doi_(identifier)):[10.1126/science.1175689](https://doi.org/10.1126%2Fscience.1175689). [PMC](/source/PMC_(identifier)) [3881419](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881419). [PMID](/source/PMID_(identifier)) [19628817](https://pubmed.ncbi.nlm.nih.gov/19628817).

- Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, et al. (January 2006). ["Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1356129). *Genome Research*. **16** (1): 55–65. [doi](/source/Doi_(identifier)):[10.1101/gr.4039406](https://doi.org/10.1101%2Fgr.4039406). [PMC](/source/PMC_(identifier)) [1356129](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1356129). [PMID](/source/PMID_(identifier)) [16344560](https://pubmed.ncbi.nlm.nih.gov/16344560).

- González-Cabo P, Vázquez-Manrique RP, García-Gimeno MA, Sanz P, Palau F (August 2005). ["Frataxin interacts functionally with mitochondrial electron transport chain proteins"](https://doi.org/10.1093%2Fhmg%2Fddi214). *Human Molecular Genetics*. **14** (15): 2091–8. [doi](/source/Doi_(identifier)):[10.1093/hmg/ddi214](https://doi.org/10.1093%2Fhmg%2Fddi214). [PMID](/source/PMID_(identifier)) [15961414](https://pubmed.ncbi.nlm.nih.gov/15961414).

- Baysal BE, Lawrence EC, Ferrell RE (March 2007). ["Sequence variation in human succinate dehydrogenase genes: evidence for long-term balancing selection on SDHA"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1852088). *BMC Biology*. **5** 12. [doi](/source/Doi_(identifier)):[10.1186/1741-7007-5-12](https://doi.org/10.1186%2F1741-7007-5-12). [PMC](/source/PMC_(identifier)) [1852088](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1852088). [PMID](/source/PMID_(identifier)) [17376234](https://pubmed.ncbi.nlm.nih.gov/17376234).

- Eng C, Kiuru M, Fernandez MJ, Aaltonen LA (March 2003). "A role for mitochondrial enzymes in inherited neoplasia and beyond". *Nature Reviews. Cancer*. **3** (3): 193–202. [doi](/source/Doi_(identifier)):[10.1038/nrc1013](https://doi.org/10.1038%2Fnrc1013). [PMID](/source/PMID_(identifier)) [12612654](https://pubmed.ncbi.nlm.nih.gov/12612654). [S2CID](/source/S2CID_(identifier)) [20549458](https://api.semanticscholar.org/CorpusID:20549458).

- Brière JJ, Favier J, El Ghouzzi V, Djouadi F, Bénit P, Gimenez AP, Rustin P (October 2005). ["Succinate dehydrogenase deficiency in human"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11139140). *Cellular and Molecular Life Sciences*. **62** (19–20): 2317–24. [doi](/source/Doi_(identifier)):[10.1007/s00018-005-5237-6](https://doi.org/10.1007%2Fs00018-005-5237-6). [PMC](/source/PMC_(identifier)) [11139140](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11139140). [PMID](/source/PMID_(identifier)) [16143825](https://pubmed.ncbi.nlm.nih.gov/16143825). [S2CID](/source/S2CID_(identifier)) [23793565](https://api.semanticscholar.org/CorpusID:23793565).

- Korsten A, de Coo IF, Spruijt L, de Wit LE, Smeets HJ, Sluiter W (February 2010). ["Patients with Leber hereditary optic neuropathy fail to compensate impaired oxidative phosphorylation"](https://doi.org/10.1016%2Fj.bbabio.2009.10.003). *Biochimica et Biophysica Acta (BBA) - Bioenergetics*. **1797** (2): 197–203. [doi](/source/Doi_(identifier)):[10.1016/j.bbabio.2009.10.003](https://doi.org/10.1016%2Fj.bbabio.2009.10.003). [PMID](/source/PMID_(identifier)) [19836344](https://pubmed.ncbi.nlm.nih.gov/19836344).

- Hendrickson SL, Lautenberger JA, Chinn LW, Malasky M, Sezgin E, Kingsley LA, et al. (September 2010). ["Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943476). *PLOS ONE*. **5** (9) e12862. [Bibcode](/source/Bibcode_(identifier)):[2010PLoSO...512862H](https://ui.adsabs.harvard.edu/abs/2010PLoSO...512862H). [doi](/source/Doi_(identifier)):[10.1371/journal.pone.0012862](https://doi.org/10.1371%2Fjournal.pone.0012862). [PMC](/source/PMC_(identifier)) [2943476](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943476). [PMID](/source/PMID_(identifier)) [20877624](https://pubmed.ncbi.nlm.nih.gov/20877624).

- Van Coster R, Seneca S, Smet J, Van Hecke R, Gerlo E, Devreese B, et al. (July 2003). "Homozygous Gly555Glu mutation in the nuclear-encoded 70 kDa flavoprotein gene causes instability of the respiratory chain complex II". *American Journal of Medical Genetics. Part A*. **120A** (1): 13–8. [doi](/source/Doi_(identifier)):[10.1002/ajmg.a.10202](https://doi.org/10.1002%2Fajmg.a.10202). [PMID](/source/PMID_(identifier)) [12794685](https://pubmed.ncbi.nlm.nih.gov/12794685). [S2CID](/source/S2CID_(identifier)) [30987591](https://api.semanticscholar.org/CorpusID:30987591).

- Wang L, McDonnell SK, Hebbring SJ, Cunningham JM, St Sauver J, Cerhan JR, et al. (December 2008). ["Polymorphisms in mitochondrial genes and prostate cancer risk"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750891). *Cancer Epidemiology, Biomarkers & Prevention*. **17** (12): 3558–66. [doi](/source/Doi_(identifier)):[10.1158/1055-9965.EPI-08-0434](https://doi.org/10.1158%2F1055-9965.EPI-08-0434). [PMC](/source/PMC_(identifier)) [2750891](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750891). [PMID](/source/PMID_(identifier)) [19064571](https://pubmed.ncbi.nlm.nih.gov/19064571).

- Huang G, Chen Y, Lu H, Cao X (February 2007). ["Coupling mitochondrial respiratory chain to cell death: an essential role of mitochondrial complex I in the interferon-beta and retinoic acid-induced cancer cell death"](https://doi.org/10.1038%2Fsj.cdd.4402004). *Cell Death and Differentiation*. **14** (2): 327–37. [doi](/source/Doi_(identifier)):[10.1038/sj.cdd.4402004](https://doi.org/10.1038%2Fsj.cdd.4402004). [PMID](/source/PMID_(identifier)) [16826196](https://pubmed.ncbi.nlm.nih.gov/16826196).

- Sifroni KG, Damiani CR, Stoffel C, Cardoso MR, Ferreira GK, Jeremias IC, et al. (September 2010). "Mitochondrial respiratory chain in the colonic mucosal of patients with ulcerative colitis". *Molecular and Cellular Biochemistry*. **342** (1–2): 111–5. [doi](/source/Doi_(identifier)):[10.1007/s11010-010-0474-x](https://doi.org/10.1007%2Fs11010-010-0474-x). [PMID](/source/PMID_(identifier)) [20440543](https://pubmed.ncbi.nlm.nih.gov/20440543). [S2CID](/source/S2CID_(identifier)) [34103232](https://api.semanticscholar.org/CorpusID:34103232).

- Ma YY, Wu TF, Liu YP, Wang Q, Li XY, Ding Y, et al. (May 2014). "Two compound frame-shift mutations in succinate dehydrogenase gene of a Chinese boy with encephalopathy". *Brain & Development*. **36** (5): 394–8. [doi](/source/Doi_(identifier)):[10.1016/j.braindev.2013.06.003](https://doi.org/10.1016%2Fj.braindev.2013.06.003). [PMID](/source/PMID_(identifier)) [23849264](https://pubmed.ncbi.nlm.nih.gov/23849264). [S2CID](/source/S2CID_(identifier)) [24730430](https://api.semanticscholar.org/CorpusID:24730430).

v t e PDB gallery 2h89: Avian Respiratory Complex II with Malonate Bound 1zp0: Crystal Structure of Mitochondrial Respiratory Complex II bound with 3-nitropropionate and 2-thenoyltrifluoroacetone 2fbw: Avian respiratory complex II with carboxin bound 1yq4: Avian respiratory complex ii with 3-nitropropionate and ubiquinone 1zoy: Crystal Structure of Mitochondrial Respiratory Complex II from porcine heart at 2.4 Angstroms 1yq3: Avian respiratory complex ii with oxaloacetate and ubiquinone 2h88: Avian Mitochondrial Respiratory Complex II at 1.8 Angstrom Resolution

v t e Oxidoreductases: CH–CH oxidoreductases (EC 1.3) 1.3.1: NAD/NADP acceptor Enoyl-acyl carrier protein reductase/Enoyl ACP reductase 7-Dehydrocholesterol reductase Biliverdin reductase 2,4 Dienoyl-CoA reductase Dihydroxymethyloxo-tetrahydroquinoline dehydrogenase 1.3.3: Oxygen acceptor Dihydroorotate dehydrogenase Coproporphyrinogen III oxidase Protoporphyrinogen oxidase Bilirubin oxidase Acyl-CoA oxidase Dihydrouracil oxidase Tetrahydroberberine oxidase Secologanin synthase Tryptophan alpha,beta-oxidase Pyrroloquinoline-quinone synthase L-galactonolactone oxidase 1.3.5: Quinone Succinate dehydrogenase SDHA SDHB SDHC SDHD 1.3.99: Other acceptors Fumarate reductase Butyryl-CoA dehydrogenase Acyl CoA dehydrogenase ACADSB ACADS 5α-reductase SRD5A1 SRD5A2 SRD5A3 Glutaryl-CoA dehydrogenase Isovaleryl coenzyme A dehydrogenase 3-oxo-5beta-steroid 4-dehydrogenase

v t e Metabolism: Citric acid cycle enzymes Cycle Citrate synthase Aconitase Isocitrate dehydrogenase Oxoglutarate dehydrogenase Succinyl CoA synthetase Succinate dehydrogenase (SDHA) Fumarase Malate dehydrogenase and ETC Anaplerotic to acetyl-CoA Pyruvate dehydrogenase complex (E1, E2, E3) (regulated by Pyruvate dehydrogenase kinase and Pyruvate dehydrogenase phosphatase) to α-ketoglutaric acid Glutamate dehydrogenase to succinyl-CoA Methylmalonyl-CoA mutase to oxaloacetic acid Pyruvate carboxylase Aspartate transaminase Mitochondrial electron transport chain/ oxidative phosphorylation Primary Complex I/NADH dehydrogenase Complex II/Succinate dehydrogenase Coenzyme Q10 (CoQ10) Complex III/Coenzyme Q - cytochrome c reductase Cytochrome c Complex IV/Cytochrome c oxidase Coenzyme Q10 synthesis: COQ2 COQ3 COQ4 COQ5 COQ6 COQ7 COQ9 COQ10A COQ10B PDSS1 PDSS2 Other Alternative oxidase Electron-transferring-flavoprotein dehydrogenase

v t e Enzymes Activity Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis Regulation Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator Classification EC number Enzyme superfamily Enzyme family List of enzymes Kinetics Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics Types EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

[Portal](https://en.wikipedia.org/wiki/Wikipedia:Contents/Portals):
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Adapted from the Wikipedia article [SDHA](https://en.wikipedia.org/wiki/SDHA) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/SDHA?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.