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T cell Activation Is Driven by an ADP-Dependent Glukosinase Linking Enhanced Glycolysis with Mitochondrial Reactive Oxygen Species Generation
Abstract
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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Authors (10)
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Marcin M. Kamiński
- DKFZ
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Sven W. Sauer
- DKFZ
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Silvana Opp
- University Children’s Hospital
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Thorsten Ruppert
- University Children’s Hospital
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Paulius Grigaravicius
- DKFZ
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Przemysław Grudnik
- Jagiellonian University
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Hermann-Josef Grone
- DKFZ
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Peter H. Krammer
- DKFZ
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Karsten Gulow
- DKFZ
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Keywords
Details
- Category:
- Articles
- Type:
- artykuły w czasopismach recenzowanych i innych wydawnictwach ciągłych
- Published in:
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Cell Reports
no. 2,
pages 1300 - 1315,
ISSN: 2211-1247 - Language:
- English
- Publication year:
- 2012
- Bibliographic description:
- 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:
- Digital Object Identifier (open in new tab) 10.1016/j.celrep.2012.10.009
- Verified by:
- Gdańsk University of Technology
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