电压依赖性阴离子通道2介导的线粒体凋亡在骨骼肌消耗中的作用

The role of voltage dependent anion channel 2 in mitochondria driven apoptosis in skeletal muscle wasting

烧伤后骨骼肌消耗严重影响烧伤患者的治疗及预后。核凋亡是骨骼肌消耗的途径之一。线粒体能放大外源性凋亡信号、并启动内源性凋亡信号,是凋亡的核心环节。电压依赖性阴离子通道(voltage dependent anion channel,VDAC)是线粒体外膜的主要蛋白,其有三个表型,其中VDAC2的功能最为重要。VDAC2对线粒体外膜透化起门控作用,可与bcl-2家族及己糖激酶等相互作用,调控细胞的凋亡与存活。因此,VDAC2可能是骨骼肌消耗机制的核心环节,具有成为骨骼肌消耗调控靶点的潜力。

Severe burns are typically followed by hypermetabolism that is characterized by significant muscle wasting （MW）, which causes considerable morbidity and mortality. Nuclear apoptosis is one important mechanism of MW. Mitochondria serves as both initiator and accelerator of apoptotic signals and is recognized as the center for the integration of apoptotic signaling. Voltage dependent anion channel （VDAC） , the major mitochondrial outer membrane protein, have three types. VDAC2 acts most importantly by functioning as gatekeeper for mitochondrial permeability transition pore. VDAC2 can interact with several proteins such as bcl-2 family proteins, hexokinase, and son on, which plays an important role in the coordination of communication between the mitochondria and the rest of the cell to regulate cell survival or apoptosis. These findings indicate that VDAC may be the core of MW and it may be a pharmacologic or regulated target.