迪斯科伊丁域受体1转移到线粒体促进氧化应激和亡在急性损伤
Gema Bolas1, Corina M Borza1, Fabian Bock1
1Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN, USA.
Journal of the American Society of Nephrology : JASN
|February 24, 2026
概括
迪斯科伊丁域受体1 (DDR1) 在急性损伤 (AKI) 中移动到线粒体,增加线粒体活性氧物种 (mtROS) 和亡. 抑制DDR1或其下游效应可以减少损伤.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 急性损伤 (AKI) 的特点是线粒体损伤和线粒体活性氧物种 (mtROS) 的增加.
- 迪斯科伊丁域受体1 (DDR1),一个原受体氨酸激酶,在AKI中发挥作用.
- 已发现DDR1与线粒体蛋白相互作用,这表明线粒体的作用.
研究的目的:
- 为了调查DDR1是否转移到AKI中的线粒体.
- 为了确定线粒体DDR1 (mitDDR1) 是否有助于线粒体功能障碍,mtROS产生和AKI中的亡.
主要方法:
- 在具有AKI的人类和小鼠脏中分析了DDR1局部化.
- 细胞表达野生型或酶死亡的DDR1被用于研究DDR1转位和功能.
- 评估了mitDDR1在调节mtROS和亡中的作用,包括其与mtHsp60和p66Shc酸化的相互作用.
主要成果:
- 在人类患者和小鼠的受伤脏中检测到mitDDR1.
- 原激活的DDR1转移到线粒体,增加mtROS的产生和管状细胞的亡.
- 这种转位涉及与mtHsp60的关联,并促进了p66Shc酸化,导致氧化应激和亡. 抑制DDR1或p66Shc酸化可以降低这些效应.
结论:
- 激活的DDR1通过一种新的非正规途径转移到线粒体.
- 这种线粒体转移促进了氧化应激和亡,有助于AKI的发病.
- 针对这种DDR1通路可能为AKI提供治疗策略.
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