Malic enzyme 3, mitochondrial (ME3)

Malic enzyme 3, mitochondrial (ME3) is a member of the malic enzyme family that facilitates the oxidative decarboxylation of malate to pyruvate, generating NADPH in the process (UniProt P40926). While ME3 is typically expressed at low levels in most adult tissues, it plays a critical role in maintaining mitochondrial redox balance and supporting cellular antioxidant defenses (Nature, 2017, 542(7639):119-123). In the context of oncology, ME3 is a prominent example of collateral lethality; in pancreatic cancers where the ME2 gene is co-deleted with the SMAD4 tumor suppressor, ME3 becomes essential for cell survival (Cancer Discovery, 2017, 7(3):242-243). Inhibiting ME3 in these specific genetic backgrounds leads to a depletion of NADPH, an increase in reactive oxygen species (ROS), and subsequent apoptosis of cancer cells. Although no ME3 inhibitors are currently FDA-approved, the enzyme is an active target for small-molecule drug discovery aimed at treating ME2-deficient malignancies (Journal of Medicinal Chemistry, 2020).

Other names

NADP-dependent malic enzyme, mitochondrialMalic enzyme 3NADP-ME3

Inhibition of the oxidative decarboxylation of malate to pyruvate to deplete mitochondrial NADPH and induce oxidative stress-mediated cell death (Nature, 2017, 542(7639):119-123).