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Mitochondrial metabolism compounds act on the respiratory chain, energy coupling and redox balance of mitochondria. In 1961 Mitchell proposed that phosphorylation is coupled to electron transfer through a chemiosmotic mechanism. In this model a proton gradient across the inner membrane drives adenosine triphosphate (ATP) synthase in oxidative phosphorylation (OXPHOS). Rotenone inhibits complex I of the electron transport chain, and oligomycin A blocks ATP synthase. Gboxin, reported in 2019, is an OXPHOS inhibitor that suppresses the growth of glioblastoma cells. Mito-TEMPO is a mitochondria-targeted antioxidant that scavenges superoxide in the matrix. Meldonium inhibits carnitine biosynthesis and so limits fatty acid transport into mitochondria. The set is mixed and also lists compounds with secondary mitochondrial links, such as the fluoroquinolone ciprofloxacin.
KL1333 is an orally available, small organic molecule that reacts with NAD(P)H:quinone oxidoreductase 1 (NQO1) as a substrate, resulting in increases in intracellular NAD+ levels via NADH oxidation. KL-1333 Improves Energy Metabolism and Mitochondrial Dysfunction in MELAS Fibroblasts.
