粒体相关内质网膜系链蛋白互作对脑缺血/再灌注的作用研究进展

Research progress on the effects of mitochondrial-associated endoplasmic reticulum membranes tethering proteins interaction on cerebral ischemia/reperfusion

脑缺血/再灌注损伤(cerebral ischemia/reperfusion injury,CIRI)是缺血性脑卒中血流再灌注引起的二次伤害,其机制复杂,涉及线粒体能量代谢障碍、Ca^(2+)超载、氧化应激、细胞凋亡、炎症反应、兴奋性氨基酸毒性、血脑屏障破坏、过量NO合成以及细胞焦亡等多个方面。线粒体相关内质网膜(mitochondrial-associated endoplasmic reticulum membranes,MAMs)是内质网中的特殊结构域,在多种细胞过程中扮演关键角色,如调节线粒体形态和活性、脂质代谢、Ca^(2+)稳态和细胞活性等。现有研究证实线粒体稳态、细胞凋亡和内质网应激均与MAMs密切相关。本文总结近年有关MAMs的研究进展,综述MAMs的生物学作用和系链蛋白的定位,剖析线粒体和内质网两个细胞器之间的信号交流,探讨MAMs系链蛋白互作对CIRI病理生理学过程中Ca^(2+)信号转导、细胞活性的影响,以期为治疗CIRI提供理论基础。

Cerebral ischemia/reperfusion injury(CIRI)refers to secondary damage caused by reperfusion of blood flow following ischemic stroke.Its mechanism is complex,involving mitochondrial energy metabolism disorders,Ca^(2+)overload,oxidative stress,apoptosis,inflammatory responses,excitatory amino acid toxicity,blood-brain barrier disruption,excessive NO synthesis,and cell necrosis etc.Mitochondrial-associated endoplasmic reticulum membranes(MAMs)are specialized regions of the endoplasmic reticulum that play crucial roles in various cellular processes,including regulation of mitochondrial morphology and activity,lipid metabolism,Ca^(2+)homeostasis,and cell viability.Existing research has confirmed that mitochondrial homeostasis,cell apoptosis,and endoplasmic reticulum stress are closely related to MAMs.This article summarizes the research progress on MAMs in recent years,reviews the biological functions of MAMs and the localization of tethering proteins,analyzes the signaling between mitochondria and the endoplasmic reticulum,explores the impact of MAMs tethering proteins interaction on Ca^(2+)signaling and cell viability during the pathophysiological process of CIRI,aiming to provide a theoretical basis for the treatment of CIRI.