Electron Transport Chain (Complex II, III, IV) Antibody Sampler Kit

Background

Succinate dehydrogenase (SDH), also known as Complex II or succinate:quinone oxidoreductase, is a key component of the citric acid cycle and the electron transport chain (ETC) (1). Specifically, it is involved in the oxidation of succinate (2). SDH consists of four subunits: SDHA, SDHB, SDHC, and SDHD (3). Ubiquinol-cytochrome c reductase iron-sulfur subunit (UQCRFS1), also known as Rieske iron-sulfur protein (RISP), is a component of Complex III in the mitochondrial ETC. UQCRFS1/RISP and two other subunits, cytochrome b (MT-CYB) and cytochrome c1 (CYC1), are essential for the catalytic activity of Complex III (4). Cytochrome c is a well conserved electron transport protein and is part of the respiratory chain localized to mitochondrial intermembrane space (5). Upon apoptotic stimulation, cytochrome c released from mitochondria associates with procaspase-9 (47 kDa)/Apaf-1. This complex processes caspase-9 from inactive proenzyme to its active form (6). This event further triggers caspase-3 activation and eventually leads to apoptosis (7). The mitochondrial ETC comprises multiple protein complexes, including cytochrome c oxidase. Cytochrome c oxidase catalyzes the reduction of oxygen to water. This process is coupled with pumping protons from the mitochondrial matrix into mitochondrial intermembrane space, contributing to the proton gradient used for ATP synthesis (8). Cytochrome c oxidase consists of 3 mitochondrial DNA-encoded subunits (COX1/MT-CO1, COX2/MT-CO2, and COX3/MT-CO3) and multiple nuclear DNA-encoded subunits (9). Research studies show that the mRNAs of the mitochondrially encoded oxidative phosphorylation subunits, including COX1/MT-CO1, decline significantly during aging (10). Cytochrome c oxidase (COX) is a hetero-oligomeric enzyme consisting of 13 subunits localized to the inner mitochondrial membrane (11-13). It is the terminal enzyme complex in the respiratory chain, catalyzing the reduction of molecular oxygen to water coupled to the translocation of protons across the mitochondrial inner membrane to drive ATP synthesis. The 3 largest subunits forming the catalytic core are encoded by mitochondrial DNA, while the other smaller subunits, including COX IV, are nuclear-encoded. Research studies have shown that deficiency in COX activity correlates with a number of human diseases (14). COX10 is an assembly factor for cytochrome c oxidase (COX, also known as Complex IV) in the mitochondrial ETC (15,16). Studies show that, when the gene encoding the β2-adrenergic receptor (Adrb2) is deleted, increased oxidative phosphorylation in endothelial cells inhibits angiogenesis. Deletion of Cox10 prevents the metabolic switch to oxidative phosphorylation in endothelial cells deleted of Adrb2, causing angiogenesis and cancer progression (16). In addition, COX10 contributes to T cell quiescence exit and is critical for T cell activation (17). Succinate dehydrogenase subunit 5 (SDH5, SDHAF2) is a subunit of the succinate dehydrogenase (SDH) protein complex responsible for the oxidation of succinate during the citric acid cycle. Mitochondrial SDH5 associates with the catalytic subunit of succinate dehydrogenase and is required for adding FAD cofactor to the SDH catalytic subunit (18). Mutations in the corresponding SDHAF2 gene are associated with hereditary head and neck paragangliomas, an autosomal disorder characterized by the development of tumors with increased penetrance over time (18). Additional research studies show that SDH5 is involved in regulation of lung cancer metastasis mediated by the glycogen synthase kinase 3β and β-catenin signaling pathways (19).