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

在揭示细胞内现象的还原论方法中,科学家们最近将注意力集中在线粒体上。细胞器具有独特的进化史和组织,被证明是重要的细胞存活开关。除了控制细胞的生物能学外,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,可作为防止胞质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对于对抗氧化应激和维持膜通透性很重要。线粒体在决定细胞对多种生理和遗传压力,细胞器间通讯以及最终细胞存活的反应中的重要性一直在本文中讨论和讨论。参与细胞凋亡和坏死细胞死亡的线粒体事件,如Bcl-2家族蛋白的激活、通透性转换孔的形成、细胞色素c和凋亡诱导因子的释放、半胱天冬酶级联的激活以及最终的细胞死亡等不仅是细胞生物学家关注的焦点,但也适用于毒理学家揭示应激反应。由ROS引起的线粒体DNA突变,其无法完全修复以及突变的恶性循环以及Bcl-2家族基因和蛋白质的作用已与许多疾病有关,其中线粒体功能障碍起着关键作用。将低分子量化合物 (包括抗氧化剂) 靶向线粒体的新治疗方法是将压力抑制在芽中的一步。

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