摘要
线粒体在细胞死亡中占有中心地位,但其他细胞器影响线粒体启动细胞死亡的机制仍不十分明确.近几年来,随着对溶酶体功能的不断了解,Alexei等提出了溶酶体线粒体轴理论.这一理论阐述了溶酶体与线粒体的相互作用,并最终导致细胞死亡的机理.各种致凋亡因素作用于溶酶体,导致溶酶体膜通透性改变.溶酶体膜通透性改变能通过铁依赖的方式、脂褐素相关的方式、Bcl-2家族依赖的方式和Rho/ROCK途径-JNK信号通路的方式影响线粒体,造成线粒体膜通透性改变,进而启动细胞死亡.而线粒体膜通透性改变能通过ROS依赖的方式和Bcl-2家族依赖的方式引起溶酶体通透性改变,最终导致细胞死亡.溶酶体线粒体轴理论还能用于解释非酒精性脂肪肝和溶酶体贮积症的发病机制.本文将对溶酶体线粒体轴理论及其与疾病的关系两方面进行阐述.
The key role of mitochondria in cell death has been widely accepted, but it remains unclear on how other organelles influence mitochondria to initiate cell death. Recently, Alexei et al. proposed a theory of lysosomal-mitochondrial axis that explained the mechanism of lysosome- mitochondria interaction based on latest studies in lysosomal functions. Apoptotic factors may permeablize the lysosomal membrane, then through iron-dependent, lipofuscin-related, Bcl-2 family-dependent, or Rho/ROCK- JNK pathways cause in the permeability of mitochondrial membrane and initiate cell death. On the other hand, mitochondrial membrane permeabilization can also permeablize the lysosomal membrane through the ROS-dependent and Bcl-2 family- dependent ways and promotes cell death. The theory of ＂lysosomal- mitochondrial axis＂ was lately being used to explain the pathogenesis of nonalcoholic fatty liver disease and the lysosomal storage diseases. This review introduces the ＂lysosomal-mitochondrial axis＂ theory and discusses it implication in disease conditions.
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2012年第10期892-896,共5页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金(No.30672480)资助~~
关键词
溶酶体线粒体轴理论
细胞死亡
溶酶体
线粒体
lysosomal-mitochondrial axis theory
cell death
lysosome
mitochondria
