Year: 2012
Type: article
Abstract: TLR agonists initiate a rapid activation program in dendritic cells (DCs) that requires support from metabolic and bioenergetic resources. We found previously that TLR signaling promotes aerobic glycolysis and a decline in oxidative phosphorylation (OXHPOS) and that glucose restriction prevents activation and leads to premature cell death. However, it remained unclear why the decrease in OXPHOS occurs under these circumstances. Using real-time metabolic flux analysis, in the present study, we show that mitochondrial activity is lost progressively after activation by TLR agonists in inflammatory blood monocyte-derived DCs that express inducible NO synthase. We found that this is because of inhibition of OXPHOS by NO and that the switch to glycolysis is a survival response that serves to maintain ATP levels when OXPHOS is inhibited. Our data identify NO as a profound metabolic regulator in inflammatory monocyte-derived DCs.
Source: Blood
Institutions: Trudeau Institute, Washington University in St. Louis
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: bronze
Awards: G1565341982, Diabetes Research & Training Center, G2051891711, Metabolic Regulation of CD8 T Cell Memory Development, A Resource for Biomedical Mass Spectrometry, Research Training in Immunology and Infectious Diseases, Dendritic Cell Function in Schistosomiasis, MANIPULATING DENDRITIC CELL METABOLISM TO PROMOTE CANCER IMMUNITY, G766674393, G87705910, Washington University Nutrition Obesity Research Center, Diabetes Research Center
OpenAlex ID: W2042849313