Mitochondrial dehydrogenase

Mitochondrial dehydrogenases are a diverse group of enzymes located within the mitochondria that catalyze the oxidation of substrates by transferring electrons to acceptors such as NAD+ or FAD (Sreedhar et al., 2020, Molecules). These enzymes are central to the tricarboxylic acid (TCA) cycle, fatty acid beta-oxidation, and the electron transport chain, making them fundamental to cellular bioenergetics and biosynthetic processes (Spinelli & Haigis, 2018, Nature Cell Biology). In clinical contexts, these enzymes are frequently targeted to combat metabolic reprogramming in cancer; for instance, devimistat inhibits the alpha-ketoglutarate dehydrogenase complex to disrupt the energy metabolism of tumor cells (Pardee et al., 2014, Expert Opinion on Investigational Drugs). Additionally, the inhibition of mitochondrial NADH dehydrogenase (Complex I) by metformin is a cornerstone in the treatment of type 2 diabetes, highlighting the therapeutic importance of this enzyme class (Wheaton et al., 2014, eLife). However, the designation "Other mitochondrial dehydrogenases" is considered an incorrect or non-specific target identifier because it serves as a collective grouping for various distinct enzymes rather than a single, well-defined molecular target (ChEMBL Database). This lack of specificity poses challenges for drug discovery and precise mechanism-of-action characterization.

Other names

Mitochondrial oxidoreductasesMitochondrial NAD(P)+-dependent dehydrogenasesMitochondrial FAD-dependent dehydrogenases

Inhibition of enzymatic redox reactions to disrupt ATP production, alter metabolic intermediates, or induce apoptosis through oxidative stress.