3.D.10.1.7
Succinate dehydrogenase complex, or succinate:ubiquinone oxidoreductase (SQR) or  mitochondrial respiratory complex II of four subunits, SdhA, B, C and D.  Does not transport protons across the membrane, but all 4 subunits are homologous to the prokaryotic Sdh subunits that do transport protons.  It is an integral membrane protein complex in both the tricarboxylic acid cycle and aerobic respiration. Sun et al. 2005 reported the first crystal structure of Complex II from porcine heart at 2.4 Å resolution and its complex structure with inhibitors 3-nitropropionate and 2-thenoyltrifluoroacetone (TTFA) at 3.5 Å resolution. Complex II is comprised of two hydrophilic proteins, flavoprotein (Fp) and iron-sulfur protein (Ip), and two transmembrane proteins (CybL and CybS), as well as prosthetic groups required for electron transfer from succinate to ubiquinone. The structure correlates the protein environments around prosthetic groups with their unique midpoint redox potentials. Two ubiquinone binding sites are identified. The structure provides a bona fide model for study of the mitochondrial respiratory system and human mitochondrial diseases related to mutations in this complex (Sun et al. 2005).  the loss of electron transfer Complex II (succcinate dehydrogenase), but not that of Complex I, reduces melanoma tumor growth by increasing antigen presentation and T cell-mediated killing. This is driven by succinate-mediated transcriptional and epigenetic activation of major histocompatibility complex-antigen processing and presentation (MHC-APP) genes independent of interferon signaling (Mangalhara et al. 2023). Curcumin induces mitophagy by promoting mitochondrial succinate dehydrogenase activity and sensitizes human papillary thyroid carcinoma BCPAP cells to radioiodine treatment (Zhang et al. 2023).  The New Nematicide Cyclobutrifluram Targets the Mitochondrial Succinate Dehydrogenase Complex in Bursaphelenchus xylophilus (Liu et al. 2024).