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Details on Person The succinate dehydrogenase complex (SDH, complex II), assoc...
| Class:Id | Summation:71411 |
|---|---|
| _displayName | The succinate dehydrogenase complex (SDH, complex II), assoc... |
| _timestamp | 2023-12-06 10:08:21 |
| modified | [InstanceEdit:198405] D'Eustachio, P, 2007-06-18 16:46:57 [InstanceEdit:9767104] Rothfels, Karen, 2022-02-24 [InstanceEdit:9854201] Stephan, Ralf, 2023-11-23 [InstanceEdit:9855644] Stephan, Ralf, 2023-12-06 |
| text | The succinate dehydrogenase complex (SDH, complex II), associated with the inner mitochondrial membrane, catalyzes the dehydrogenation of succinate to fumarate, reducing ubiquinone (Q10) to ubiquinol (Q10H2) on the membrane part of the enzyme. FAD is covalently bound to His-99 of the SDHA subunit (PDB 6VAX; Sharma et al., 2020). The redox potential of Q10H2 is then used in the electron transfer chain to drive a proton motive force to generate ATP (Devertanian et al., 1964; Renkema et al., 2015) The endogenous metabolite itaconate has been shown to bind and inhibit Complex II, leading to an accumulation of succinate. Elevated succinate levels modulate immune, hypoxic and metabolic reprogramming pathways, including during oncogenesis (Booth et al, 1952; Selak et al., 2005; Cordes et al., 2016; reviewed by Hayash et al., 2018; Peace & O'Neill, 2022). The mitochondrial heat shock protein 75 kDa (TRAP1) inhibits Complex II which elicits respiratory downregulation, leading to a pseudohypoxic state. This state is caused by succinate-dependent HIF1-alpha stabilisation which, in turn, can promote tumorigenesis (Sciacovelli et al. 2013, Yoshida et al. 2013, Guzzo et al. 2014). Mutations in all four SDH subunits (SDHA, SDHB, SDHC, SDHD) have been reported, leading to distinct phenotypes of SDH deficiency and tumors (reviewed by Briere et al., 2005). |
| (summation) | [Reaction:70994] SDH complex dehydrogenates succinate [Homo sapiens] |
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