Autor: |
Inés Romero-Carramiñana, Sonia Dominguez-Zorita, Pau B. Esparza-Moltó, José M. Cuezva |
Jazyk: |
angličtina |
Rok vydání: |
2024 |
Předmět: |
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Zdroj: |
iScience, Vol 27, Iss 6, Pp 109863- (2024) |
Druh dokumentu: |
article |
ISSN: |
2589-0042 |
DOI: |
10.1016/j.isci.2024.109863 |
Popis: |
Summary: T cells experience metabolic reprogramming to an enhanced glycolysis upon activation. Herein, we have investigated whether ATPase Inhibitory Factor 1 (IF1), the physiological inhibitor of mitochondrial ATP synthase, participates in rewiring T cells to a particular metabolic phenotype. We show that the activation of naive CD4+ T lymphocytes both in vitro and in vivo is accompanied by a sharp upregulation of IF1, which is expressed only in Th1 effector cells. T lymphocytes of conditional CD4+-IF1-knockout mice display impaired glucose uptake and flux through glycolysis, reducing the biogenesis of mitochondria and cellular proliferation after activation. Consequently, mice devoid of IF1 in T lymphocytes cannot mount an effective Th1 response against bacterial infection compromising their survival. Overall, we show that the inhibition of a fraction of ATP synthase by IF1 regulates metabolic reprogramming and functionality of T cells, highlighting the essential role of IF1 in adaptive immune responses. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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