biostudies-literatureCircu MLNIDDK NIH HHSNational Institutes of Health16-24https://www.ebi.ac.uk/biostudies/studies/S-EPMC5345695biostudies-literatureUnknown264In this study, we investigated how colonic epithelial cells maintained pyridine nucleotide (NADH/NAD⁺) redox homeostasis upon acute metabolic variation imposed by glucose deprivation or supplementation with mitochondrial substrates, succinate and malate/glutamate (M/G). Our results showed that low glucose caused cellular NADH/NAD⁺ redox imbalance that diminished lactate dehydrogenase (LDH) activity and resulted in lower lactate contents. The concurrent activation of malic enzyme (ME) suggested a role for malate in preserving cellular pyruvate that remained unchanged at low glucose. Mitochondrial substrates restored cellular NADH/NAD⁺ redox homeostasis at low glucose in association with specific compartmental catabolism of mitochondrial substrates. As compared with normal glucose, M/G and low glucose promoted glycolytic ATP production but inhibited mitochondrial-derived ATP generation in association with decreased glucose availability for mitochondrial respiration. At normal glucose, succinate and M/G enhanced mitochondrial respiratory activity, but had minimal impact on mitochondrial-derived ATP production. Collectively, these results are consistent with low glucose-induced NADH/NAD⁺ redox imbalance in association with decreased aerobic glycolysis that is reversed by supplementation with M/G but not succinate.Chemico-biological interactionsLow glucose stress decreases cellular NADH and mitochondrial ATP in colonic epithelial cancer cells: Influence of mitochondrial substrates.PMC5345695R01 DK044510Aw TYMaloney RECircu MLfalseLow glucose stress decreases cellular NADH and mitochondrial ATP in colonic epithelial cancer cells: Influence of mitochondrial substrates.In this study, we investigated how colonic epithelial cells maintained pyridine nucleotide (NADH/NAD⁺) redox homeostasis upon acute metabolic variation imposed by glucose deprivation or supplementation with mitochondrial substrates, succinate and malate/glutamate (M/G). Our results showed that low glucose caused cellular NADH/NAD⁺ redox imbalance that diminished lactate dehydrogenase (LDH) activity and resulted in lower lactate contents. The concurrent activation of malic enzyme (ME) suggested a role for malate in preserving cellular pyruvate that remained unchanged at low glucose. Mitochondrial substrates restored cellular NADH/NAD⁺ redox homeostasis at low glucose in association with specific compartmental catabolism of mitochondrial substrates. As compared with normal glucose, M/G and low glucose promoted glycolytic ATP production but inhibited mitochondrial-derived ATP generation in association with decreased glucose availability for mitochondrial respiration. At normal glucose, succinate and M/G enhanced mitochondrial respiratory activity, but had minimal impact on mitochondrial-derived ATP production. Collectively, these results are consistent with low glucose-induced NADH/NAD⁺ redox imbalance in association with decreased aerobic glycolysis that is reversed by supplementation with M/G but not succinate.2017-01-01T00:00:00Z2017 Feb2024-11-12T08:08:23.478Z2019-03-26T23:03:13ZS-EPMC53456952808746110.1016/j.cbi.2017.01.001