Mitophagy programs: mechanisms and physiological implications of mitochondrial targeting by autophagy.
Mitophagy programs: mechanisms and physiological implications of mitochondrial targeting by autophagy.
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DOI：
10.1007/s00018-015-2087-8
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发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Brady NR
中科院分区：
文献类型：
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作者：
Hamacher-Brady A;Brady NR
线粒体是细胞功能ATP的重要来源，但当线粒体受损时，会产生过多的应激信号，导致细胞功能障碍，最终导致程序性细胞死亡。因此，维持细胞稳态的一个主要组成部分是通过自噬介导的降解（即线粒体自噬）来识别和去除功能失调的线粒体。线粒体自噬进一步构成了一个发育过程，并与细胞凋亡发生高度的相互作用。线粒体质量控制的减少与疾病发病机制有关，这表明过程阐明作为临床靶点的重要性。最近的研究表明，线粒体自噬过程中存在多个独立或相互作用的程序，需要线粒体外膜自噬受体活性的调节。在这里，我们回顾了这些线粒体自噬程序，重点介绍了识别和靶向线粒体被自噬体隔离的途径机制，以及控制途径活性的机制。此外，我们还介绍了目前可用的检测有丝分裂的方法。
Mitochondria are an essential source of ATP for cellular function, but when damaged, mitochondria generate a plethora of stress signals, which lead to cellular dysfunction and eventually programmed cell death. Thus, a major component of maintaining cellular homeostasis is the recognition and removal of dysfunctional mitochondria through autophagy-mediated degradation, i.e., mitophagy. Mitophagy further constitutes a developmental program, and undergoes a high degree of crosstalk with apoptosis. Reduced mitochondrial quality control is linked to disease pathogenesis, suggesting the importance of process elucidation as a clinical target. Recent work has revealed multiple mitophagy programs that operate independently or undergo crosstalk, and require modulated autophagy receptor activities at outer membranes of mitochondria. Here, we review these mitophagy programs, focusing on pathway mechanisms which recognize and target mitochondria for sequestration by autophagosomes, as well as mechanisms controlling pathway activities. Furthermore, we provide an introduction to the currently available methods for detecting mitophagy.