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KL1333 (NQO1 activator 1) enhances energy metabolism and mitochondrial dysfunction in MELAS fibroblasts. Elevated NAD+ levels trigger the activation of SIRT1 and AMPK, and subsequently activates PGC-1α. NQO1 activator 1 is an orally available NAD+ modulator. It reacts with NAD(P)H: NQO1 as a substrate, resulting in increases in intracellular NAD+ levels via NADH oxidation.