低氧诱导线粒体自噬的机制及其在相关疾病中的研究进展

Mechanisms of hypoxia-induced mitophagy and its advances in related diseases

线粒体在氧充足的条件下通过氧化磷酸化产生三磷酸腺苷供应机体的能量代谢.当细胞低氧时,线粒体产生大量的活性氧（ROS）,导致氧化应激和线粒体功能障碍,从而对组织或细胞造成损伤,导致疾病发生.因此,降低体内的ROS水平对控制疾病、维持机体内稳态至关重要.近些年研究显示细胞在低氧条件下可通过上调低氧诱导因子1、激活BNIP3和BNIP3L/NIX介导的通路、线粒体上FU NDC1受体的可逆磷酸化等机制调控线粒体自噬,清除多余的或受损的线粒体,最终减少ROS的产生.相对地,ROS自身可激活其他多种信号分子,如p62、FOXO3等对细胞自噬进行调节.低氧诱导ROS的损害作用及线粒体自噬的保护作用与呼吸疾病、代谢疾病、肿瘤及神经退行性疾病等疾病密切相关,深入研究低氧诱导线粒体自噬的具体机制有可能为疾病的诊治提供新的方向.本文就低氧诱导线粒体自噬发生的机制及其与相关疾病的关联作一综述.

Mitochondria produce adenosine triphosphate under oxygen sufficient conditions through oxidative phosphorylation to supply energy metabolism of the body.When the cells are in hypoxia, mitochondria can produces a number of reactive oxygen species （ROS）,causing oxidative stress and mitochondrial dysfunction,which damages tissues or cells and causes diseases.Therefore,reducing the level of ROS in vivo is essential to maintain the homeostasis of the body.Recent studies have shown that cells can regulate mitophagy under hypoxic conditions by up-regulating hypoxia-inducible factor 1, activation of BNIP3,BNIP3L/NIX-mediated pathways,and reversible phosphorylation of FUNDC 1 receptors,further remove excess or damaged mitochondria,and ultimately reduce the production of ROS. In contrast,ROS can activate a variety of other signal molecules,such as p62 and FOXO3,to regulate cell autophagy.And the related studies have shown that mitophagy is closely related to respiratory diseases, endocrine,tumors,neurological diseases and other diseases.This paper reviews the progress of pathegenesis of hypoxia-induced mitophagy and its relevance to the related diseases.