This study presents a method to improve energy metabolism and provides a valuable thinking to enhance virus vaccine production. These results revealed that over-expression of Aralar I can improve the energy metabolism of PK15 cells and also enhance the replication of the PCV2 virus in PK15 cells. Finally, compared with the PCV2 yield of infected control PK15 cells, the PCV2 yield of infected Aralar I over-expression cells was enhanced by 42.5% ( p < 0.05). Furthermore, the glutamine consumption rate increased by 36.4% ( p < 0.01). Genetic, pharmacological and metabolomics experiments reveal that the malateaspartate shuttle and mitochondrial citrate export support the differentiation of mouse T helper 1 cells, whereas. The ATP/ADP ratio and O 2 uptake rate also increased by 39% ( p < 0.05) and 37.8% ( p < 0.01), respectively. The elevated glycolysis in cancer cells is proposed to be one of the mechanisms acquired to accelerate oxidative. Compared with control PK15 cells, lactate accumulation in Aralar I over-expressing cells decreased by 44.8% ( p < 0.01), whereas the mitochondrial NADH and pyruvate concentrations increased by 50% ( p < 0.05) and 35.4% ( p < 0.05), respectively. Aspartate is transported out of the mitochondria and released into the extracellular space from synaptic microvesicles. We demonstrated that the malate-aspartate shuttle exerts control over NAD /NADH homeostasis to maintain activity of mitochondrial lactate dehydrogenase and to enable aerobic oxidation of glycolytic l-lactate in mitochondria. Recently, we over-expressed the human malate–aspartate NADH shuttle member Aralar I in PK15 cells to enhance proliferation of PCV2. However, production of an attenuated PCV2 vaccine has not been satisfactory. All rights reserved.The considerable losses sustained by the pig industry due to porcine circovirus-2 (PCV2) could be avoided by using an attenuated vaccine. Overall, we show that the MAS is important for de novo serine biosynthesis, implying that serine supplementation could be used as a therapeutic strategy for MAS defects and possibly other redox disorders.ĬP: Metabolism NADH shuttle central carbon metabolism glycolysis isotope-tracer analysis malate dehydrogenase malate-aspartate shuttle metabolomics serine biosynthesis.Ĭopyright © 2023 The Authors. Increasing the NAD +-regenerating capacity using pyruvate supplementation resolves most of the metabolic disturbances. Among the MAS-deficient cells, those lacking malate dehydrogenase 1 (MDH1) show the most severe metabolic disruptions, whereas oxoglutarate-malate carrier (OGC)- and MDH2-deficient cells are less affected. MAS-deficient cells have reduced serine biosynthesis, which strongly correlates with the lactate M+3/pyruvate M+3 ratio (reflective of the cytosolic NAD +/NADH ratio), consistent with the NAD + dependency of phosphoglycerate dehydrogenase in the serine synthesis pathway. We genetically disrupted each MAS component to generate a panel of MAS-deficient HEK293 cell lines in which we performed -glucose tracing. Electronic address: malate-aspartate shuttle (MAS) is a redox shuttle that transports reducing equivalents across the inner mitochondrial membrane while recycling cytosolic NADH to NAD +. 6 Department of Genetics, Section Metabolic Diagnostics, University Medical Center Utrecht, LundlEA Utrecht, the Netherlands. ![]()
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