Succinate dehydrogenase (SDH) (SDH)

Succinate dehydrogenase (SDH), also known as mitochondrial complex II or succinate-ubiquinone oxidoreductase, is a unique heterotetrameric enzyme complex located in the inner mitochondrial membrane [1, 2]. It serves a dual role in cellular metabolism, functioning as a key component of both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain (ETC) [4, 12]. The complex consists of four nuclear-encoded subunits (SDHA, SDHB, SDHC, and SDHD) and catalyzes the oxidation of succinate to fumarate while simultaneously transferring electrons to the ubiquinone pool [2, 15]. Mutations in SDH subunits are strongly associated with various hereditary cancers, such as paragangliomas and pheochromocytomas, due to the accumulation of the oncometabolite succinate [14, 15]. Additionally, SDH is a major target for agricultural fungicides (SDHIs) and is being explored as a therapeutic target for ischemia-reperfusion injury and inflammatory diseases [7, 16, 17]. Pharmacological inhibition of SDH can lead to metabolic rewiring and increased reactive oxygen species production, which has implications for both toxicity and therapeutic intervention [13, 16].

Other names

Mitochondrial complex IISuccinate-ubiquinone oxidoreductaseSuccinate:ubiquinone oxidoreductaseSuccinate-coenzyme Q reductaseSQRComplex IICII

Inhibition of the enzymatic conversion of succinate to fumarate and the subsequent transfer of electrons to the mitochondrial ubiquinone pool, thereby disrupting both the tricarboxylic acid cycle and the electron transport chain.