Modulation of mitochondrial membrane permeability in pathogenesis, autophagy and control of metabolism
Modulation of mitochondrial membrane permeability in pathogenesis, autophagy and control of metabolism
复制标题
DOI：
10.1111/j.1440-1746.2006.04643.x
复制
发表时间：
2007-06-01
影响因子：
4.1
通讯作者：
Lemasters, John J.
中科院分区：
文献类型：
--
作者：
Lemasters, John J.
线粒体内膜和外膜具有相反的渗透性特征。外膜对所有低分子量溶质是非特异性渗透的，而内膜除了通过特异性转运蛋白外是不可渗透的。在压力之后，有时在正常生理状态下，两种膜的渗透性可以逆转。在内膜中，渗透性转换孔打开以引起线粒体渗透性转换（MPT）。随着MPT涉及越来越多的线粒体，自噬、凋亡和坏死逐渐发展，与线粒体损伤的比例和三磷酸腺苷（ATP）耗尽的程度相关，这是一种坏死现象。与此相反，外膜可能会降低其渗透性后，一定的压力，通过关闭电压依赖性阴离子通道（VDAC）。VDAC闭合全面抑制线粒体功能，以防止缺氧-缺血中无效的ATP水解，并可能在氧化应激条件下释放有毒的超氧化物。VDAC封闭还可以促进乙醇暴露后乙醛的选择性氧化，并促进癌细胞中的有氧糖酵解。相比之下，VDAC开放被提出刺激氧化磷酸化并促进葡萄糖刺激的胰腺β细胞的胰岛素释放。因此，VDAC充当线粒体功能的全局调节器或管理器。了解这些线粒体膜通透性的变化本身是如何调节的仍然不完整，需要进一步的研究。
The mitochondrial inner and outer membranes have contrasting permeability characteristics. The outer membrane is non-specifically permeable to all low-molecular-weight solutes, whereas the inner membrane is impermeable except through specific transporters. After stresses and sometimes in normal physiology, the permeability of the two membranes can reverse. In the inner membrane, permeability transition pores open to cause the mitochondrial permeability transition (MPT). As the MPT involves more and more mitochondria, autophagy, apoptosis and necrosis progressively develop linked to the proportion of mitochondria injured and the extent of adenosine triphosphate (ATP) depletion, a phenomenon of necrapoptosis. By contrast, the outer membrane may decrease its permeability after certain stresses via closure of voltage-dependent anion channels (VDAC). The VDAC closure globally suppresses mitochondrial function to prevent futile ATP hydrolysis in hypoxia-ischemia and possibly the release of toxic superoxide under conditions of oxidative stress. The VDAC closure may also facilitate selective oxidation of acetaldehyde after ethanol exposure and promote aerobic glycolysis in cancer cells. By contrast, VDAC opening is proposed to stimulate oxidative phosphorylation and promote insulin release by glucose-stimulated pancreatic beta cells. Thus, VDAC serves as a global regulator, or governator, of mitochondrial function. Understanding of how these mitochondrial membrane permeability changes are themselves regulated remains incomplete and requires future study.