title: Low glucose stress decreases cellular NADH and mitochondrial ATP in colonic epithelial cancer cells: Influence of mitochondrial substrates.
abstract: 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.
authors.affiliation: Department of Molecular & Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA; Department of Medicine, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA, USA. Electronic address: mmarac@lsuhsc.edu.
authors.forename: Magdalena L
authors.initials: ML
authors.lastname: Circu
authors.affiliation: Department of Molecular & Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Maloney
authors.affiliation: Department of Molecular & Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors.forename: Tak Yee
authors.initials: TY
authors.lastname: Aw
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006019:Glycolysis; D019073:HT29 Cells; D006801:Humans; D008293:Malates / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D019802:Succinic Acid / Q000378:metabolism
chemical_list: D008293:Malates; D009243:NAD; D018698:Glutamic Acid; C030298:malic acid; D000255:Adenosine Triphosphate; D019802:Succinic Acid; D005947:Glucose
keywords: Cellular/compartmental NADH/NAD(+); Glucose stress; HT29; Mitochondrial substrates