In their reductionist approach in unraveling phenomena inside the cell, scientists in recent times have focused attention to mitochondria. An organelle with peculiar evolutionary history and organization, it is turning out to be an important cell survival switch. Besides controlling bioenergetics of a cell it also has its own genetic machinery which codes 37 genes. It is a major source of generation of reactive oxygen species, acts as a safety device against toxic increases of cytosolic Ca2+ and its membrane permeability transition is a critical control point in cell death. Redox status of mitochondria is important in combating oxidative stress and maintaining membrane permeability. Importance of mitochondria in deciding the response of cell to multiplicity of physiological and genetic stresses, inter-organelle communication, and ultimate cell survival is constantly being unraveled and discussed in this review. Mitochondrial events involved in apoptosis and necrotic cell death, such as activation of Bcl-2 family proteins, formation of permeability transition pore, release of cytochrome c and apoptosis inducing factors, activation of caspase cascade, and ultimate cell death is the focus of attention not only for cell biologists, but also for toxicologists in unraveling stress responses. Mutations caused by ROS to mitochondrial DNA, its inability to repair it completely and creation of a vicious cycle of mutations along with role of Bcl-2 family genes and proteins has been implicated in many diseases where mitochondrial dysfunctions play a key role. New therapeutic approaches toward targeting low molecular weight compounds to mitochondria, including antioxidants is a step toward nipping the stress in the bud.

译文

:最近,科学家们以还原论的方法揭示了细胞内部的现象,将注意力集中在线粒体上。具有独特的进化历史和组织的细胞器,事实证明它是重要的细胞存活开关。除了控制细胞的生物能,它还具有自己的遗传机制,可编码37个基因。它是产生活性氧的主要来源,是防止细胞溶质Ca2毒性增加的安全装置,其膜通透性转变是细胞死亡的关键控制点。线粒体的氧化还原状态在抵抗氧化应激和维持膜通透性方面很重要。在决定细胞对多种生理和遗传压力,细胞间通讯以及最终细胞存活的反应中,线粒体的重要性正在不断地被探讨和讨论。涉及凋亡和坏死细胞死亡的线粒体事件,例如Bcl-2家族蛋白的激活,通透性过渡孔的形成,细胞色素c和凋亡诱导因子的释放,胱天蛋白酶级联的激活以及最终细胞死亡等,不是人们关注的焦点。不仅适用于细胞生物学家,还适用于毒理学家,以阐明压力反应。 ROS引起的线粒体DNA突变,其无法完全修复,突变的恶性循环以及Bcl-2家族基因和蛋白质的作用,在许多疾病中都与线粒体功能障碍起着关键作用。将低分子量化合物靶向线粒体(包括抗氧化剂)的新治疗方法是消除发芽压力的一步。

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