NLRX1 dampens oxidative stress and apoptosis in tissue injury via control of mitochondrial activity
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- Geurt Stokman
- Department of Pathology, Academic Medical Center, Amsterdam, Netherlands 1
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- Lotte Kors
- Department of Pathology, Academic Medical Center, Amsterdam, Netherlands 1
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- Pieter J. Bakker
- Department of Pathology, Academic Medical Center, Amsterdam, Netherlands 1
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- Elena Rampanelli
- Department of Pathology, Academic Medical Center, Amsterdam, Netherlands 1
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- Nike Claessen
- Department of Pathology, Academic Medical Center, Amsterdam, Netherlands 1
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- Gwendoline J.D. Teske
- Department of Pathology, Academic Medical Center, Amsterdam, Netherlands 1
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- Loes Butter
- Department of Pathology, Academic Medical Center, Amsterdam, Netherlands 1
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- Harmen van Andel
- Department of Pathology, Academic Medical Center, Amsterdam, Netherlands 1
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- Marius A. van den Bergh Weerman
- Department of Pathology, Academic Medical Center, Amsterdam, Netherlands 1
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- Per W.B. Larsen
- Department of Pathology, Academic Medical Center, Amsterdam, Netherlands 1
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- Mark C. Dessing
- Department of Pathology, Academic Medical Center, Amsterdam, Netherlands 1
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- Coert J. Zuurbier
- Department of Anaesthesiology, Academic Medical Center, Amsterdam, Netherlands 2
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- Stephen E. Girardin
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada 3
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- Sandrine Florquin
- Department of Pathology, Academic Medical Center, Amsterdam, Netherlands 1
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- Jaklien C. Leemans
- Department of Pathology, Academic Medical Center, Amsterdam, Netherlands 1
抄録
<jats:p>Mitochondrial dysfunction is the most prominent source of oxidative stress in acute and chronic kidney disease. NLRX1 is a receptor of the innate immune system that is ubiquitously expressed and localized in mitochondria. We investigated whether NLRX1 may act at the interface of metabolism and innate immunity in a model of oxidative stress. Using a chimeric mouse model for renal ischemia-reperfusion injury, we found that NLRX1 protects against mortality, mitochondrial damage, and epithelial cell apoptosis in an oxidative stress–dependent fashion. We found that NLRX1 regulates oxidative phosphorylation and cell integrity, whereas loss of NLRX1 results in increased oxygen consumption, oxidative stress, and subsequently apoptosis in epithelial cells during ischemia-reperfusion injury. In line, we found that NLRX1 expression in human kidneys decreased during acute renal ischemic injury and acute cellular rejection. Although first implicated in immune regulation, we propose that NLRX1 function extends to the control of mitochondrial activity and prevention of oxidative stress and apoptosis in tissue injury.</jats:p>
収録刊行物
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- Journal of Experimental Medicine
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Journal of Experimental Medicine 214 (8), 2405-2420, 2017-06-16
Rockefeller University Press