Malic enzyme 3 (NADP(+)-dependent, mitochondrial) mRNA (ME3 mRNA)

Malic enzyme 3 (ME3) is a mitochondrial enzyme that catalyzes the oxidative decarboxylation of malate to pyruvate, producing NADPH in the process (UniProt P40926). In the context of oncology, ME3 mRNA has been identified as a prime candidate for collateral lethality, particularly in pancreatic ductal adenocarcinoma (PDAC) where the ME2 gene is often deleted as part of the SMAD4 locus (Dey et al., Nature, 2017). Because ME2 and ME3 perform redundant functions in maintaining mitochondrial NADPH pools, cells lacking ME2 become hypersensitive to the depletion of ME3 (PubMed: 28102844). Targeting ME3 mRNA using tools like siRNA or antisense oligonucleotides (ASOs) disrupts redox homeostasis and leads to selective cancer cell death (Cancer Discovery, 2017). This approach offers a therapeutic window by exploiting genetic deletions that are specific to the tumor, potentially minimizing toxicity to healthy tissues that express ME2.

Other names

NADP-dependent malic enzyme, mitochondrial mRNAME3Malic enzyme 3 mRNA

RNA interference-mediated degradation of ME3 mRNA or antisense-mediated inhibition of translation, leading to the depletion of mitochondrial malic enzyme 3 protein levels.