通过AMPK介导的RIPK1酸化进行细胞死亡的代谢调节
Tao Zhang1, Daichao Xu2,3, Elijah Trefts4
1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Science (New York, N.Y.)
|June 29, 2023
概括
通过抑制RIPK1, 在能量压力期间防止细胞死亡. 这一代谢检查点将细胞命运,代谢和炎症整合起来.
科学领域:
- 细胞生物学
- 代谢过程
- 分子生物学
背景情况:
- 氨酸单酸激活蛋白激酶 (AMPK) 调节了对能量压力的代谢适应.
- 持续的代谢压力可能导致细胞死亡,但AMPK在这个过程中的作用尚不清楚.
- 受体相互作用蛋白激酶1 (RIPK1) 激活与压力诱导的细胞死亡有关.
研究的目的:
- 阐明AMPK在代谢压力下影响细胞死亡的机制.
- 研究AMPK,RIPK1和细胞命运决定之间的相互作用.
- 确定与代谢压力相关的潜在治疗点.
主要方法:
- 研究了对代谢应激反应中的AMPK和RIPK1激活.
- 使用基因操纵 (Ampk缺陷,RIPK1 S415A突变) 来评估功能后果.
- 使用小鼠缺血损伤模型来评估体内相关性.
主要成果:
- 代谢压力通过TRAIL受体激活RIPK1.
- 通过在Ser415上化,AMPK抑制了RIPK1的激活,从而抑制了细胞死亡.
- Ampk 缺乏或 RIPK1 S415A 突变促进了 RIPK1 的激活和细胞死亡.
- 在Ampkα1缺乏的小鼠中,对抗缺血性损伤的基因RIPK1失活.
结论:
- RIPK1的AMPK酸化是控制细胞在压力下的关键代谢检查点.
- AMPK-RIPK1轴整合了新陈代谢,细胞死亡和炎症.
- 这一轴代表了涉及代谢压力和细胞死亡的疾病的新疗法目标.
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