The mitochondrial NADH pool is involved in hydrogen sulfide signaling and stimulation of aerobic glycolysis
| Autor: | Allison Maebius, Roshan Kumar, Ruma Banerjee, Victor Vitvitsky, Marouane Libiad, Aaron P. Landry |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
sulfide quinone oxidoreductase LbNOX Lactobacillus brevis NADH oxidase Sulfide Hydrogen sulfide ETC electron transport chain hydrogen sulfide TCA tricarboxylic acid Sulfur metabolism DPBS modified PBS Oxidative phosphorylation Pentose phosphate pathway Biochemistry 03 medical and health sciences chemistry.chemical_compound FBS fetal bovine serum Humans SQOR sulfide quinone oxidoreductase aerobic glycolysis Molecular Biology chemistry.chemical_classification DMEM Dulbecco's modified Eagle's medium 030102 biochemistry & molecular biology Chemistry electron transport chain Cell Biology HCT116 Cells NAD equipment and supplies Electron transport chain Mitochondria Citric acid cycle 030104 developmental biology Anaerobic glycolysis Glycolysis HT29 Cells Signal Transduction Research Article |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1016/j.jbc.2021.100736 |
| Popis: | Hydrogen sulfide is synthesized by enzymes involved in sulfur metabolism and oxidized via a dedicated mitochondrial pathway that intersects with the electron transport chain at the level of complex III. Studies with H2S are challenging since it is volatile and also reacts with oxidized thiols in the culture medium, forming sulfane sulfur species. The half-life of exogenously added H2S to cultured cells is unknown. In this study, we first examined the half-life of exogenously added H2S to human colonic epithelial cells. In plate cultures, H2S disappeared with a t1/2 of 3 to 4 min at 37 °C with a small fraction being trapped as sulfane sulfur species. In suspension cultures, the rate of abiotic loss of H2S was slower, and we demonstrated that sulfide stimulated aerobic glycolysis, which was sensitive to the mitochondrial but not the cytoplasmic NADH pool. Oxidation of mitochondrial NADH using the genetically encoded mito-LbNOX tool blunted the cellular sensitivity to sulfide-stimulated aerobic glycolysis and enhanced its oxidation to thiosulfate. In contrast, sulfide did not affect flux through the oxidative pentose phosphate pathway or the TCA cycle. Knockdown of sulfide quinone oxidoreductase, which commits H2S to oxidation, sensitized cells to sulfide-stimulated aerobic glycolysis. Finally, we observed that sulfide decreased ATP levels in cells. The dual potential of H2S to activate oxidative phosphorylation at low concentrations, but inhibit it at high concentrations, suggests that it might play a role in tuning electron flux and, therefore, cellular energy metabolism, particularly during cell proliferation. |
| Databáze: | OpenAIRE |
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