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Furthermore, pyruvate dehydrogenase complex can translocate from the mitochondria to the nucleus (in a manner still unclear) during cell-cycle progression, generating a nuclear pool of acetyl-CoA from pyruvate and increasing the acetylation of core histones important for S phase entry as well as expression of damage-response genes among others (82

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Here, we have reported the discovery of two allosteric ME2 inhibitors, EA and MDSA, that are capable of inhibiting ME2 activity and thus decreasing the production of cellular pyruvate, NADH, and ATP