IDH is a key enzyme in the tricarboxylic acid (TCA) cycle. It catalyzes the oxidative decarboxylation of isocitrate to a-ketoglutarate (a-KG) and CO2, which is accompanied by the reduction of NAD(P1) to NAD(P)H. The IDH reaction provides organisms with not only energy but also biosynthetic precursors, such as a-KG, for metabolism. Thus, these metabolic pathways are among the first to have evolved1,2. Consequently, IDHs are ubiquitously distributed throughout the three domains of life: Archaea, Bacteria, and Eukarya. Based on coenzyme specificity, the IDH family can be divided into NAD1-dependent IDHs (EC 1.1.1.41, NAD-IDHs) and NADP1-dependent IDHs (EC 1.1.1.41, NADP-IDHs). IDHs with different coenzyme dependencies play varying roles in vivo. NAD-IDH catalysis generates NADH, which participates in energy metabolism. NADP-IDH catalysis generates NADPH, which is an important source of reducing power. NADPH also plays a role in the cellular defense against oxidative damage and the detoxification of reactive oxygen species3–5.