NLRX1 dampens oxidative stress and apoptosis in tissue injury via control of mitochondrial activity

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 innat...

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Bibliographic Details
Published in:The Journal of experimental medicine 2017-08, Vol.214 (8), p.2405-2420
Main Authors: Stokman, Geurt, Kors, Lotte, Bakker, Pieter J, Rampanelli, Elena, Claessen, Nike, Teske, Gwendoline J D, Butter, Loes, van Andel, Harmen, van den Bergh Weerman, Marius A, Larsen, Per W B, Dessing, Mark C, Zuurbier, Coert J, Girardin, Stephen E, Florquin, Sandrine, Leemans, Jaklien C
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - physiology
Cellular manufacture
Disease Models, Animal
Epithelial cells
Humans
Immune system
Immunity
Immunoregulation
Injury prevention
Innate immunity
Ischemia
Ischemia - physiopathology
Kidney - blood supply
Kidney - metabolism
Kidney - physiopathology
Kidneys
Male
Metabolism
Mice, Inbred C57BL
Mitochondria
Mitochondria - physiology
Mitochondrial Proteins - physiology
Oxidative phosphorylation
Oxidative stress
Oxidative Stress - physiology
Oxygen consumption
Phosphorylation
Reactive oxygen species
Reperfusion
Reperfusion Injury - physiopathology
Rodents
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Summary: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.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20161031