electron transport complex ii


Summary: A flavoprotein oxidase complex that contains iron-sulfur centers. It catalyzes the oxidation of SUCCINATE to fumarate and couples the reaction to the reduction of UBIQUINONE to ubiquinol.

Top Publications

  1. Colle D, Santos D, Hartwig J, Godoi M, Braga A, Farina M. Succinobucol versus probucol: higher efficiency of succinobucol in mitigating 3-NP-induced brain mitochondrial dysfunction and oxidative stress in vitro. Mitochondrion. 2013;13:125-33 pubmed publisher
    ..The present findings suggest that succinobucol might be a novel strategy to slow or halt oxidative events in neurodegenerative conditions. ..
  2. Bayley J, Devilee P, Taschner P. The SDH mutation database: an online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency. BMC Med Genet. 2005;6:39 pubmed
  3. Janeway K, Kim S, Lodish M, Nose V, Rustin P, Gaal J, et al. Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. Proc Natl Acad Sci U S A. 2011;108:314-8 pubmed publisher
    ..Testing for germline mutations in SDH is recommended in patients with WT GIST. These findings highlight a potential central role of SDH dysregulation in WT GIST oncogenesis. ..
  4. Korpershoek E, Favier J, Gaal J, Burnichon N, van Gessel B, Oudijk L, et al. SDHA immunohistochemistry detects germline SDHA gene mutations in apparently sporadic paragangliomas and pheochromocytomas. J Clin Endocrinol Metab. 2011;96:E1472-6 pubmed publisher
    ..A recent report described a patient with an abdominal paraganglioma, immunohistochemically negative for SDHA, and identified a causal germline mutation in SDHA...
  5. Szeto S, Reinke S, Sykes B, Lemire B. Ubiquinone-binding site mutations in the Saccharomyces cerevisiae succinate dehydrogenase generate superoxide and lead to the accumulation of succinate. J Biol Chem. 2007;282:27518-26 pubmed
    ..We suggest that SDH mutations can promote tumor formation by contributing to both reactive oxygen species production and to a proliferative response normally induced by hypoxia via the accumulation of succinate. ..
  6. Augereau O, Claverol S, Boudes N, Basurko M, Bonneu M, Rossignol R, et al. Identification of tyrosine-phosphorylated proteins of the mitochondrial oxidative phosphorylation machinery. Cell Mol Life Sci. 2005;62:1478-88 pubmed
    ..The tyrosine phosphatase PTP 1B was found in brain but not in muscle, heart or liver mitochondria. Our results suggest that tyrosine kinases and phosphatases are involved in the regulation of oxidative phosphorylation...
  7. Piruat J, Pintado C, Ortega Saenz P, Roche M, Lopez Barneo J. The mitochondrial SDHD gene is required for early embryogenesis, and its partial deficiency results in persistent carotid body glomus cell activation with full responsiveness to hypoxia. Mol Cell Biol. 2004;24:10933-40 pubmed
    ..They also suggest that, contrary to previous beliefs, mitochondrial complex II is not directly involved in CB oxygen sensing. ..
  8. Bugiani M, Lamantea E, Invernizzi F, Moroni I, Bizzi A, Zeviani M, et al. Effects of riboflavin in children with complex II deficiency. Brain Dev. 2006;28:576-81 pubmed
    ..Riboflavin supplementation to the growth medium of cultured fibroblasts resulted in a 2-fold increase of complex II activity in patients, but not in controls. ..
  9. Burnichon N, Briere J, Libe R, Vescovo L, Rivière J, Tissier F, et al. SDHA is a tumor suppressor gene causing paraganglioma. Hum Mol Genet. 2010;19:3011-20 pubmed publisher
    ..The SDHA gene should be added to the list of genes encoding tricarboxylic acid cycle proteins that act as tumor suppressor genes and can now be considered as a new paraganglioma/pheochromocytoma susceptibility gene. ..

More Information


  1. Paranagama M, Sakamoto K, Amino H, Awano M, Miyoshi H, Kita K. Contribution of the FAD and quinone binding sites to the production of reactive oxygen species from Ascaris suum mitochondrial complex II. Mitochondrion. 2010;10:158-65 pubmed publisher
    ..suum adult worm together with the absence of complexes III and IV activities in its respiratory chain, it is a good model to examine the reactive oxygen species production from the mitochondrial complex II...
  2. Mueller E, Mayr J, Zimmermann F, Feichtinger R, Stanger O, Sperl W, et al. Reduction of nuclear encoded enzymes of mitochondrial energy metabolism in cells devoid of mitochondrial DNA. Biochem Biophys Res Commun. 2012;417:1052-7 pubmed publisher
    ..This finding indicates the existence of a feedback mechanism in ?(0) cells that downregulates the expression of entirely nuclear encoded components of mitochondrial energy metabolism. ..
  3. Pagnamenta A, Hargreaves I, Duncan A, Taanman J, Heales S, Land J, et al. Phenotypic variability of mitochondrial disease caused by a nuclear mutation in complex II. Mol Genet Metab. 2006;89:214-21 pubmed
    ..Comparable activities and stability of mitochondrial respiratory chain enzymes were demonstrated in both patients, so other reasons for the phenotypic variability are considered. ..
  4. Wojtovich A, NEHRKE K, Brookes P. The mitochondrial complex II and ATP-sensitive potassium channel interaction: quantitation of the channel in heart mitochondria. Acta Biochim Pol. 2010;57:431-4 pubmed
    ..4 % of total complex II molecules are necessary to activate the mK(ATP). These results estimate the mK(ATP) content at 15 channels per mitochondrion. ..
  5. Li Z, Shokes J, Kounosu A, Imai T, Iwasaki T, Scott R. X-ray absorption spectroscopic analysis of reductive [2Fe-2S] cluster degradation in hyperthermophilic archaeal succinate:caldariellaquinone oxidoreductase subunits. Biochemistry. 2003;42:15003-8 pubmed
  6. Bizat N, Hermel J, Boyer F, Jacquard C, Creminon C, Ouary S, et al. Calpain is a major cell death effector in selective striatal degeneration induced in vivo by 3-nitropropionate: implications for Huntington's disease. J Neurosci. 2003;23:5020-30 pubmed
    ..This suggests that calpain may play an important role in HD pathogenesis and could be a potential therapeutic target to slow disease progression. ..
  7. Quinlan C, Orr A, Perevoshchikova I, Treberg J, ACKRELL B, Brand M. Mitochondrial complex II can generate reactive oxygen species at high rates in both the forward and reverse reactions. J Biol Chem. 2012;287:27255-64 pubmed publisher
    ..We suggest that complex II may be an important contributor to physiological and pathological ROS production. ..
  8. Henrich M, Paddenberg R, Haberberger R, Scholz A, Gruss M, Hempelmann G, et al. Hypoxic increase in nitric oxide generation of rat sensory neurons requires activation of mitochondrial complex II and voltage-gated calcium channels. Neuroscience. 2004;128:337-45 pubmed
  9. Wittig I, Carrozzo R, Santorelli F, Schagger H. Functional assays in high-resolution clear native gels to quantify mitochondrial complexes in human biopsies and cell lines. Electrophoresis. 2007;28:3811-20 pubmed
  10. Tomitsuka E, Goto Y, Taniwaki M, Kita K. Direct evidence for expression of type II flavoprotein subunit in human complex II (succinate-ubiquinone reductase). Biochem Biophys Res Commun. 2003;311:774-9 pubmed
  11. Huang L, Sun G, Cobessi D, Wang A, Shen J, Tung E, et al. 3-nitropropionic acid is a suicide inhibitor of mitochondrial respiration that, upon oxidation by complex II, forms a covalent adduct with a catalytic base arginine in the active site of the enzyme. J Biol Chem. 2006;281:5965-72 pubmed
  12. Gimenez Roqueplo A, Favier J, Rustin P, Rieubland C, Kerlan V, Plouin P, et al. Functional consequences of a SDHB gene mutation in an apparently sporadic pheochromocytoma. J Clin Endocrinol Metab. 2002;87:4771-4 pubmed
    ..This observation highlights the role of the complex II mitochondrial genes in the oxygen-sensing pathway and in the regulation of angiogenesis of neural crest-derived tumors. ..
  13. Yankovskaya V, Horsefield R, T rnroth S, Luna Chavez C, Miyoshi H, L ger C, et al. Architecture of succinate dehydrogenase and reactive oxygen species generation. Science. 2003;299:700-4 pubmed publisher
    ..Furthermore, symptoms of genetic disorders associated with mitochondrial SQR mutations may be a result of ROS formation resulting from impaired electron transport in the enzyme...
  14. Benard G, Faustin B, Passerieux E, Galinier A, Rocher C, Bellance N, et al. Physiological diversity of mitochondrial oxidative phosphorylation. Am J Physiol Cell Physiol. 2006;291:C1172-82 pubmed
    ..To conclude, we submitted our data to a principal component analysis that revealed three groups of tissues: muscle and heart, brain, and liver and kidney. ..
  15. Iverson T, Maklashina E, Cecchini G. Structural basis for malfunction in complex II. J Biol Chem. 2012;287:35430-8 pubmed publisher
    ..These analyses provide clues to the molecular basis for diseases associated with aberrant complex II function. ..
  16. Weissmann N, Zeller S, Schäfer R, Turowski C, Ay M, Quanz K, et al. Impact of mitochondria and NADPH oxidases on acute and sustained hypoxic pulmonary vasoconstriction. Am J Respir Cell Mol Biol. 2006;34:505-13 pubmed
  17. Bayley J, Kunst H, Cascon A, Sampietro M, Gaal J, Korpershoek E, et al. SDHAF2 mutations in familial and sporadic paraganglioma and phaeochromocytoma. Lancet Oncol. 2010;11:366-72 pubmed publisher
    ..Dutch Cancer Society, European Union 6th Framework Program, Fondo Investigaciones Sanitarias, Fundación Mutua Madrileña, and Red Temática de Investigación Cooperativa en Cáncer. ..
  18. Gebert N, Gebert M, Oeljeklaus S, von der Malsburg K, Stroud D, Kulawiak B, et al. Dual function of Sdh3 in the respiratory chain and TIM22 protein translocase of the mitochondrial inner membrane. Mol Cell. 2011;44:811-8 pubmed publisher
    ..We conclude that the assembly of Sdh3 with different partner proteins, Sdh4 and Tim18, recruits it to two different mitochondrial membrane complexes with functions in bioenergetics and protein biogenesis, respectively. ..
  19. Pantaleo M, Astolfi A, Indio V, Moore R, Thiessen N, Heinrich M, et al. SDHA loss-of-function mutations in KIT-PDGFRA wild-type gastrointestinal stromal tumors identified by massively parallel sequencing. J Natl Cancer Inst. 2011;103:983-7 pubmed publisher
    ..This is the first report, to our knowle dge, that identifies SDHA inactivation as a common oncogenic event in GISTs that lack a mutation in KIT and PDGFRA. ..
  20. Benchoua A, Trioulier Y, Zala D, Gaillard M, Lefort N, Dufour N, et al. Involvement of mitochondrial complex II defects in neuronal death produced by N-terminus fragment of mutated huntingtin. Mol Biol Cell. 2006;17:1652-63 pubmed
    ..The present results strongly suggest that complex II defects in HD may be instrumental in striatal cell death. ..
  21. Majumder P, Raychaudhuri S, Chattopadhyay B, Bhattacharyya N. Increased caspase-2, calpain activations and decreased mitochondrial complex II activity in cells expressing exogenous huntingtin exon 1 containing CAG repeat in the pathogenic range. Cell Mol Neurobiol. 2007;27:1127-45 pubmed
  22. Wittig I, Karas M, Schagger H. High resolution clear native electrophoresis for in-gel functional assays and fluorescence studies of membrane protein complexes. Mol Cell Proteomics. 2007;6:1215-25 pubmed
    ..The advantages of high resolution clear native electrophoresis make this technique superior for functional proteomics analyses. ..
  23. Chen Y, McMillan Ward E, Kong J, Israels S, Gibson S. Mitochondrial electron-transport-chain inhibitors of complexes I and II induce autophagic cell death mediated by reactive oxygen species. J Cell Sci. 2007;120:4155-66 pubmed
    ..These results indicate that targeting mETC complex I and II selectively induces autophagic cell death through a ROS-mediated mechanism. ..
  24. Tran Q, Rothery R, Maklashina E, Cecchini G, Weiner J. The quinone binding site in Escherichia coli succinate dehydrogenase is required for electron transfer to the heme b. J Biol Chem. 2006;281:32310-7 pubmed
    ..Overall, these results demonstrate the importance of a functional, semiquinone-stabilizing Q(P) site for the observation of rapid succinate-dependent heme reduction. ..
  25. Miyadera H, Shiomi K, Ui H, Yamaguchi Y, Masuma R, Tomoda H, et al. Atpenins, potent and specific inhibitors of mitochondrial complex II (succinate-ubiquinone oxidoreductase). Proc Natl Acad Sci U S A. 2003;100:473-7 pubmed
    ..Therefore, atpenins may be useful tools for clarifying the biochemical and structural properties of complex II, as well as for determining its physiological roles in mammalian tissues. ..
  26. Douwes Dekker P, Hogendoorn P, Kuipers Dijkshoorn N, Prins F, van Duinen S, Taschner P, et al. SDHD mutations in head and neck paragangliomas result in destabilization of complex II in the mitochondrial respiratory chain with loss of enzymatic activity and abnormal mitochondrial morphology. J Pathol. 2003;201:480-6 pubmed
    ..These results indicate that the function of mitochondrial complex II is compromised in the majority of head and neck paragangliomas. ..
  27. Levitas A, Muhammad E, Harel G, Saada A, Caspi V, Manor E, et al. Familial neonatal isolated cardiomyopathy caused by a mutation in the flavoprotein subunit of succinate dehydrogenase. Eur J Hum Genet. 2010;18:1160-5 pubmed publisher
  28. Benchoua A, Trioulier Y, Diguet E, Malgorn C, Gaillard M, Dufour N, et al. Dopamine determines the vulnerability of striatal neurons to the N-terminal fragment of mutant huntingtin through the regulation of mitochondrial complex II. Hum Mol Genet. 2008;17:1446-56 pubmed publisher
    ..This novel pathway links dopamine signaling and regulation of mCII activity and could play a key role in oxidative energy metabolism and explain the vulnerability of the striatum in neurodegenerative diseases. ..
  29. Tomitsuka E, Hirawake H, Goto Y, Taniwaki M, Harada S, Kita K. Direct evidence for two distinct forms of the flavoprotein subunit of human mitochondrial complex II (succinate-ubiquinone reductase). J Biochem. 2003;134:191-5 pubmed
    ..Interestingly, one of the Fp isoforms was encoded as an intronless gene. ..
  30. Eng C, Kiuru M, Fernandez M, Aaltonen L. A role for mitochondrial enzymes in inherited neoplasia and beyond. Nat Rev Cancer. 2003;3:193-202 pubmed
    ..Understanding this link between inherited cancer syndromes and neurological disease could provide further insights into the mechanisms by which mitochondrial deficiencies lead to tumour development. ..
  31. Kluckova K, Bezawork Geleta A, Rohlena J, Dong L, Neuzil J. Mitochondrial complex II, a novel target for anti-cancer agents. Biochim Biophys Acta. 2013;1827:552-64 pubmed publisher
    ..This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease. ..
  32. Ruprecht J, Iwata S, Rothery R, Weiner J, Maklashina E, Cecchini G. Perturbation of the quinone-binding site of complex II alters the electronic properties of the proximal [3Fe-4S] iron-sulfur cluster. J Biol Chem. 2011;286:12756-65 pubmed publisher
    ..Steady state enzyme kinetic characterization of the mutant enzymes shows that the redox properties of the [3Fe-4S] cluster have only a minor effect on catalysis. ..
  33. Horsefield R, Yankovskaya V, Törnroth S, Luna Chavez C, Stambouli E, Barber J, et al. Using rational screening and electron microscopy to optimize the crystallization of succinate:ubiquinone oxidoreductase from Escherichia coli. Acta Crystallogr D Biol Crystallogr. 2003;59:600-2 pubmed
    ..7, c = 521.9 A, and diffract to 2.6 A resolution. The optimization strategy used for obtaining well diffracting SQR crystals is applicable to a wide range of membrane proteins. ..
  34. Maklashina E, Cecchini G. The quinone-binding and catalytic site of complex II. Biochim Biophys Acta. 2010;1797:1877-82 pubmed publisher
    ..These data suggest that movement of the quinone within the quinone-binding pocket is essential for catalysis. ..
  35. Murray J, Marusich M, Capaldi R, Aggeler R. Focused proteomics: monoclonal antibody-based isolation of the oxidative phosphorylation machinery and detection of phosphoproteins using a fluorescent phosphoprotein gel stain. Electrophoresis. 2004;25:2520-5 pubmed
  36. Sun F, Huo X, Zhai Y, Wang A, Xu J, Su D, et al. Crystal structure of mitochondrial respiratory membrane protein complex II. Cell. 2005;121:1043-57 pubmed
    ..The Complex II structure provides a bona fide model for study of the mitochondrial respiratory system and human mitochondrial diseases related to mutations in this complex. ..
  37. Kurokawa T, Sakamoto J. Purification and characterization of succinate:menaquinone oxidoreductase from Corynebacterium glutamicum. Arch Microbiol. 2005;183:317-24 pubmed
    ..This situation may have arisen due to the horizontal gene transfer. ..
  38. Ruprecht J, Yankovskaya V, Maklashina E, Iwata S, Cecchini G. Structure of Escherichia coli succinate:quinone oxidoreductase with an occupied and empty quinone-binding site. J Biol Chem. 2009;284:29836-46 pubmed publisher
  39. Seo H, Kim W, Isacson O. Compensatory changes in the ubiquitin-proteasome system, brain-derived neurotrophic factor and mitochondrial complex II/III in YAC72 and R6/2 transgenic mice partially model Huntington's disease patients. Hum Mol Genet. 2008;17:3144-53 pubmed publisher
    ..Changes in HD patients for UPS function, BDNF expression and MCII/III activity are only partially modeled in R6/2 and YAC72 mice, with the latter at 16 months of age being most congruent with the human disease. ..
  40. Dröse S. Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning. Biochim Biophys Acta. 2013;1827:578-87 pubmed publisher
    ..This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease. ..
  41. Guzy R, Sharma B, Bell E, Chandel N, Schumacker P. Loss of the SdhB, but Not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis. Mol Cell Biol. 2008;28:718-31 pubmed
    ..Therefore, differences in ROS production, HIF proliferation, and cell proliferation contribute to the differences in tumor phenotype in cells lacking SdhB as opposed to those lacking SdhA. ..
  42. Wegrzyn J, Potla R, Chwae Y, Sepuri N, Zhang Q, Koeck T, et al. Function of mitochondrial Stat3 in cellular respiration. Science. 2009;323:793-7 pubmed publisher
    ..These data indicate that Stat3 is required for optimal function of the ETC, which may allow it to orchestrate responses to cellular homeostasis...
  43. Lastres Becker I, Bizat N, Boyer F, Hantraye P, Brouillet E, Fernandez Ruiz J. Effects of cannabinoids in the rat model of Huntington's disease generated by an intrastriatal injection of malonate. Neuroreport. 2003;14:813-6 pubmed
  44. Christenson A, Gustavsson T, Gorton L, Hägerhäll C. Direct and mediated electron transfer between intact succinate:quinone oxidoreductase from Bacillus subtilis and a surface modified gold electrode reveals redox state-dependent conformational changes. Biochim Biophys Acta. 2008;1777:1203-10 pubmed publisher
    ..When both hemes were reduced, and Q(d) was blocked by HQNO, quinone-mediated communication via the Q(p) site was no longer possible, revealing a redox-dependent conformational change in the membrane anchor domain. ..
  45. Cascon A, Ruiz Llorente S, Cebrian A, Telleria D, Rivero J, Diez J, et al. Identification of novel SDHD mutations in patients with phaeochromocytoma and/or paraganglioma. Eur J Hum Genet. 2002;10:457-61 pubmed
    ..The involvement of SDHD mutations in familial phaeochromocytoma and/or paraganglioma predisposition is of considerable interest since other studies have shown these alterations to be associated with highly expressed angiogenic factors. ..
  46. Miyadera H, Hiraishi A, Miyoshi H, Sakamoto K, Mineki R, Murayama K, et al. Complex II from phototrophic purple bacterium Rhodoferax fermentans displays rhodoquinol-fumarate reductase activity. Eur J Biochem. 2003;270:1863-74 pubmed
    ..The results strongly indicate that R. fermentans complex II and mitochondrial QFR might have evolved independently, although they both utilize RQ for fumarate reduction. ..
  47. Horsefield R, Yankovskaya V, Sexton G, Whittingham W, Shiomi K, Omura S, et al. 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. J Biol Chem. 2006;281:7309-16 pubmed
    ..This allows us to propose a mechanism for the reduction of ubiquinone during the catalytic turnover of the enzyme. ..
  48. Liot G, Bossy B, Lubitz S, Kushnareva Y, Sejbuk N, Bossy Wetzel E. Complex II inhibition by 3-NP causes mitochondrial fragmentation and neuronal cell death via an NMDA- and ROS-dependent pathway. Cell Death Differ. 2009;16:899-909 pubmed publisher
    ..These results improve our understanding of the cellular mechanisms underlying HD pathogenesis. ..
  49. Mazzucco C, Hamatake R, Colonno R, Tenney D. Entecavir for treatment of hepatitis B virus displays no in vitro mitochondrial toxicity or DNA polymerase gamma inhibition. Antimicrob Agents Chemother. 2008;52:598-605 pubmed
    ..In summary, cell culture and enzymatic studies yielded no evidence that would predict mitochondrial toxicity of ETV at exposure levels in excess of those expected to be achieved clinically. ..
  50. Wojtovich A, Smith C, Haynes C, NEHRKE K, Brookes P. Physiological consequences of complex II inhibition for aging, disease, and the mKATP channel. Biochim Biophys Acta. 2013;1827:598-611 pubmed publisher
    ..This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease. ..
  51. Guo J, Lemire B. The ubiquinone-binding site of the Saccharomyces cerevisiae succinate-ubiquinone oxidoreductase is a source of superoxide. J Biol Chem. 2003;278:47629-35 pubmed
    ..Our data also challenge the dogma that superoxide production by SDH is a flavin-mediated event rather than a quinone-mediated one. ..
  52. Cecchini G. Function and structure of complex II of the respiratory chain. Annu Rev Biochem. 2003;72:77-109 pubmed
    ..Exciting recent developments in relation to disease in humans and the formation of reactive oxygen species by complex II point to its overall importance in cellular physiology. ..
  53. Bacsi A, Woodberry M, Widger W, Papaconstantinou J, Mitra S, Peterson J, et al. Localization of superoxide anion production to mitochondrial electron transport chain in 3-NPA-treated cells. Mitochondrion. 2006;6:235-44 pubmed
    ..These results indicate that in the presence of 3-NPA, mitochondria generate O2- from a site between the ubiquinol pool and the 3-NPA block in the respiratory complex II. ..