线粒体膜通透性转换孔分子结构与功能的研究现状

Research Status of Molecular Structure and Function of Mitochondrial Permeability Transition Pore

线粒体作为真核生物产生ATP的生物能量中心,同时也是细胞死亡的主要调节途径。而线粒体膜通透性转换孔(mPTP)对维持正常线粒体稳态及促进细胞死亡具有重要意义。因此,抑制mPTP或抑制激活mPTP的线粒体钙或活性氧的增加可减少mPTP开放,从而减少细胞死亡。然而由于缺乏对形成mPTP的分子模型和工作机制的了解,抑制mPTP还存在一定限制。尽管mPTP存在几种候选分子,但随着基因敲除等技术的发展,其中大部分的分子被排除。近年来,经过低温电子显微镜的观察确定了F_(1)F_(o)-ATP合酶以及重新定义腺嘌呤核苷酸转运体在mPTP形成中的重要作用,多孔复合通道的提出为最终确定mPTP的结构和功能提供了更多研究方向。

Mitochondria,as the biological energy center for ATP production in eukaryotes,are also the main regulatory pathway of cell death.The mitochondrial permeability transition pore(mPTP)has significant physiological significance in maintaining normal mitochondrial homeostasis and promoting cell death.Therefore,the opening of mPTP can be reduced by inhibiting mPTP or inhibiting the increase of mitochondrial calcium or reactive oxygen species that activate mPTP,thereby reducing cell death.However,due to a lack of understanding of the molecular model and working mechanism for the formation of mPTP,there are still certain limitations in inhibiting mPTP.Although there are several candidate molecules for mPTP,most of them have been excluded with the development of technologies such as gene knockout.In recent years,with the observation of cryogenic electron microscopy,the important role of F_(1)F_(o)-ATP synthase in the formation of mPTP has been confirmed,and the important role of adenine nucleotide translocator in the formation of mPTP has been redefined,the proposal of the multiple-pore channels provides more research interests for the final determination of the structure and function of mPTP.