T cell Activation Is Driven by an ADP-Dependent Glukosinase Linking Enhanced Glycolysis with Mitochondrial Reactive Oxygen Species Generation - Publikacja - MOST Wiedzy

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T cell Activation Is Driven by an ADP-Dependent Glukosinase Linking Enhanced Glycolysis with Mitochondrial Reactive Oxygen Species Generation

Abstrakt

Mitochondria-originating reactive oxygen species control T cell receptor (TCR)-induced gene expression. Here, we show that TCR-triggered activation of ADP-dependent glucokinase (ADPGK), an alternative, glycolytic enzyme typical for Archaea, mediates generation of the oxidative signal. We also show that ADPGK is localized in the endoplasmic reticulum and suggest that its active site protrudes toward the cytosol. The ADPGK-driven increase in glycolytic metabolism coincides with TCR-induced glucose uptake, downregulation of mitochondrial respiration, and deviation of glycolysis toward mitochondrial glycerol-3-phosphate dehydrogenase (GPD) shuttle; i.e., a metabolic shift to aerobic glycolysis similar to the Warburg effect. The activation of respiratory-chain-associated GPD2 results in hyperreduction of ubiquinone and reactive oxygen species release from mitochondria. In parallel, mitochondrial bioenergetics and ultrastructure are altered. Downregulation of ADPGK or GPD2 abundance inhibits oxidative signal generation and induction of NF-κB-dependent gene expression, whereas overexpression of ADPGK potentiates them.

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Wersja publikacji
Accepted albo Published Version
Licencja
Creative Commons: CC-BY-NC-ND otwiera się w nowej karcie

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Kategoria:
Publikacja w czasopiśmie
Typ:
artykuły w czasopismach recenzowanych i innych wydawnictwach ciągłych
Opublikowano w:
Cell Reports nr 2, strony 1300 - 1315,
ISSN: 2211-1247
Język:
angielski
Rok wydania:
2012
Opis bibliograficzny:
Kamiński M. M., Sauer S. W., Kamiński M. A., Opp S., Ruppert T., Grigaravicius P., Grudnik P., Grone H., Krammer P. H., Gulow K.: T cell Activation Is Driven by an ADP-Dependent Glukosinase Linking Enhanced Glycolysis with Mitochondrial Reactive Oxygen Species Generation// Cell Reports. -Vol. 2., iss. 5 (2012), s.1300-1315
DOI:
Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1016/j.celrep.2012.10.009
Weryfikacja:
Politechnika Gdańska

wyświetlono 222 razy

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