线粒体治疗：一种新型的线粒体相关疾病的生物疗法

Mitochondrial therapy: a new strategy for treating mitochondrion-associated diseases

摘要:

线粒体是细胞内的一种多功能细胞器，主要负责能量产生、细胞凋亡等生命过程。线粒体缺陷与临床上百种疾病相关。越来越多的研究已表明，细胞外的线粒体可被细胞内吞，进入到细胞内，然后以完整的形态发挥作用。研究发现，线粒体是对氧含量和酸碱度极为敏感的细胞器，细胞内环境可影响线粒体的功能。外源线粒体进入到生理环境中的细胞后，将提高细胞能量供应、促进细胞存活；但线粒体进入到缺氧和酸性的肿瘤组织后，将大量产生氧自由基、诱发细胞死亡。线粒体这种环境响应性的药理特性，可应用于清除肿瘤细胞、恢复受损组织的功能。目前线粒体已用于治疗中枢神经系统疾病 (帕金森氏病、抑郁症、精神分裂症等)、外周系统疾病 (缺血性心肌损伤、脂肪肝、肺气肿等) 和肿瘤等，为线粒体相关疾病的治疗提供了新的方法。文中对这种新型生物治疗方法的研究进展、医学应用和存在的挑战进行综述。

Abstract:

Mitochondrion is a multifunctional organelle in cells and responsible for energy production, cell apoptosis and various life processes. Dysfunctional mitochondria are associated with hundreds of diseases. Increasing evidences have shown that extracellular mitochondria can be endocytosed by cells, directly into cells, and then play roles in cells. Mitochondria are the organelles that are extremely sensitive to oxygen content and pH of microenvironment that induces the adverse effect based on the cellular environment: mitochondria will increase cell survival and viability when they arrive in cells of physiological environment, but mitochondria will cause cell death when they enter the hypoxic and acidic tumor tissues, because they can produce a large amounts of oxygen free radicals. The pharmacological feature of environmental responsiveness of mitochondria could make them as a potential biological drug to kill cancer cells and restore the function of damaged tissues. Currently, mitochondria are used in the treatment of central nervous system diseases (Parkinson’s disease, depression, schizophrenia, etc.), peripheral system diseases (ischemic myocardial injury, fatty liver, emphysema, etc.) and tumor. In this review, we summarize the research progress, medical application and challenges of mitochondrial therapy.