Open AccessGlycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity
Author(s) -
Ke Xu,
Na Yin,
Min Peng,
Efstathios G. Stamatiades,
Amy Shyu,
Peng Li,
Xian Zhang,
H. Mytrang,
Zhaoquan Wang,
Kristelle J. Capistrano,
Chun Chou,
Andrew G. Levine,
Alexander Y. Rudensky,
Ming O. Li
Publication year - 2021
Publication title -
science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 12.556
H-Index - 1186
eISSN - 1095-9203
pISSN - 0036-8075
DOI - 10.1126/science.abb2683
Subject(s) - bolster , microbiology and biotechnology , phosphoinositide 3 kinase , glycolysis , immunity , signal transduction , biology , pi3k/akt/mtor pathway , immunology , metabolism , immune system , biochemistry , engineering , mechanical engineering
A metabolic circuit in T cell immunity Naïve T cells are metabolically reprogrammed when they differentiate into T effector (Teff ) cells, transitioning from a reliance on mitochondrial oxidative phosphorylation to aerobic glycolysis. Xuet al. found that lactate dehydrogenase A (LDHA), a glycolytic enzyme that converts pyruvate to lactate, is a key player in this process. Teff cells that differentiate in mice infected with the bacteriumListeria monocytogenes turned on LDHA through phosphoinositide 3-kinase (PI3K) signaling. By promoting adenosine triphosphate (ATP) production, LDHA in turn facilitated PI3K-dependent inactivation of the transcription factor Foxo1 needed for effective Teff cell responses. Thus, glycolytic ATP acts like a rheostat that both gauges and regulates PI3K-dependent signaling. This type of positive feedback circuit may also provide a mechanistic explanation for the Warburg effect observed in cancer cells.Science , this issue p.405
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