Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity Journal Article
| Authors: | Xu, K.; Yin, N.; Peng, M.; Stamatiades, E. G.; Shyu, A.; Li, P.; Zhang, X.; Do, M. H.; Wang, Z.; Capistrano, K. J.; Chou, C.; Levine, A. G.; Rudensky, A. Y.; Li, M. O. |
| Article Title: | Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity |
| Abstract: | Infection triggers expansion and effector differentiation of T cells specific for microbial antigens in association with metabolic reprograming. We found that the glycolytic enzyme lactate dehydrogenase A (LDHA) is induced in CD8+ T effector cells through phosphoinositide 3-kinase (PI3K) signaling. In turn, ablation of LDHA inhibits PI3K-dependent phosphorylation of Akt and its transcription factor target Foxo1, causing defective antimicrobial immunity. LDHA deficiency cripples cellular redox control and diminishes adenosine triphosphate (ATP) production in effector T cells, resulting in attenuated PI3K signaling. Thus, nutrient metabolism and growth factor signaling are highly integrated processes, with glycolytic ATP serving as a rheostat to gauge PI3K-Akt-Foxo1 signaling in the control of T cell immunity. Such a bioenergetic mechanism for the regulation of signaling may explain the Warburg effect. © 2021 American Association for the Advancement of Science. All rights reserved. |
| Keywords: | signaling; enzyme activity; immunity; cell; reaction kinetics; gauge; cell component |
| Journal Title: | Science |
| Volume: | 371 |
| Issue: | 6527 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2021-01-22 |
| Start Page: | 405 |
| End Page: | 410 |
| Language: | English |
| DOI: | 10.1126/science.abb2683 |
| PUBMED: | 33479154 |
| PROVIDER: | scopus |
| PMCID: | PMC8380312 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2021 -- Source: Scopus |
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