线粒体质量控制失调与恶性肿瘤发生和发展相关性的研究进展

Research Progress of Mitochondrial Quality Control Dysregulation Involving in Carcinogenesis and Tumor Progression

线粒体活性氧增多、线粒体DNA突变和拷贝数改变、Ca^(2+)超载、凋亡异常等功能障碍与肿瘤发生、生长、侵袭、转移密切相关.随着研究的逐渐深入,人们认识到线粒体是个动态的细胞器,在生理、病理因素刺激下,经线粒体融合/分裂、线粒体自噬、线粒体生物合成以及线粒体分子伴侣和线粒体未折叠蛋白反应的协同调控,在细胞器和分子水平达到对线粒体及其蛋白质的质量控制,限制和延缓功能受损线粒体的积累和过度增多,维持线粒体数量、形态、功能和蛋白质量的动态平衡,保证细胞正常生命活动的进行,使其更好地适应环境.若线粒体及其蛋白的稳态调节能力下降或失衡,会导致受损线粒体的积累并引发细胞内环境的紊乱,影响线粒体功能的正常发挥,从而诱导正常细胞的恶性转化.

Mitochondria are important intracellular organelles that not only provide energy for cellular activities via oxidative phosphorylation, but also closely associated with some important biological processes, including cell metabolism, stress signaling induction, calcium homeostasis, production of reactive oxygen species（ROS） and apoptosis.Mitochondrial dysfunction will lead to tumor development, growth, invasion and metastasis.Mitochondrial quality control system has become a key mechanism that maintains the normal function of the mitochondria, which is mainly composed of organellar and molecular control.Organellar quality control was coordinately modulated by mitochondrial fusion/fission, mitophagy and mitochondrial biogenesis.Meanwhile,molecular quality control was regulated by mitochondrial molecular chaperones and mitochondrial unfolded protein response to achieve mitochondrial protein homeostasis.In normal circumstances, mitochondrial quality control system limits the accumulation of dysfunctional mitochondria and maintains mitochondrial quantity,morphology and protein function in stable state, which was called mitochondrial homeostasis.If the mitochondrial homeostasis is impaired, increased number of injured mitochondria in cells will lead to the disturbance of intracellular homeostasis and induce malignant transformation of normal cells.