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Furthermore, mitochondrial NADPH production is dependent on at least 5 mitochondrial enzymes including nicotinamide nucleotide transhydrogenase (NNT), isocitrate dehydrogenase 2 (IDH2), malic enzyme 3 (ME3), mitochondrial homolog of 10-formyltetrahydrofolate dehydrogenase (ALDH1L2) and methylenetetrahydrofolate dehydrogenase 1 like (MTHFD1L) (4)