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.

译文

线粒体功能障碍是急性和慢性肾脏疾病中最主要的氧化应激源。 NLRX1是先天免疫系统的受体,在线粒体中普遍表达和定位。我们调查了NLRX1是否可能在氧化应激模型中的新陈代谢和先天免疫的界面上起作用。使用针对肾缺血-再灌注损伤的嵌合小鼠模型,我们发现NLRX1以氧化应激依赖性的方式防止死亡,线粒体损伤和上皮细胞凋亡。我们发现NLRX1调节氧化磷酸化和细胞完整性,而NLRX1的缺失导致缺血再灌注损伤期间上皮细胞的耗氧量增加,氧化应激和随后的细胞凋亡。一致地,我们发现在急性肾缺血性损伤和急性细胞排斥期间,人肾脏中的NLRX1表达降低。尽管首先涉及免疫调节,但我们认为NLRX1功能扩展到线粒体活性的控制以及组织损伤中氧化应激和细胞凋亡的预防。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录