Healthy mitochondria play an essential role in energy metabolism, but dysfunctional mitochondria can cause perturbations in cellular processes which can ultimately lead to cell death. The process which selectively removes and degrades dysfunctional mitochondria, mitophagy, protects against the accumulation of abnormal mitochondria and hence has a protective role in maintaining cell health. Increasing numbers of studies have linked defective mitophagy to a range of diseases, including Parkinson's disease (PD). Whilst current treatment strategies in PD can improve the classical motor symptoms of the disease, they are also associated with often severe side-effects, and generally do not tackle the underlying progressive neurodegeneration seen in the disease. The identification of novel treatment targets, such as mitophagy, are therefore of increasing interest in PD research. This review will begin by outlining the process of mitophagy, before examining evidence implicating mitophagy in both monogenic and sporadic forms of PD, drawing links between mitophagy and wider pathological processes such as protein accumulation and neuroinflammation. Finally, this review will examine the diverse strategies employed to promote mitophagy so far, discuss considerations arising from these studies, and present a framework for eventual assessment of mitophagy-promoting compounds and their viability as a treatment strategy for PD patients.

中文翻译：

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帕金森病中的线粒体自噬：从发病机制到治疗目标。

健康的线粒体在能量代谢中起着至关重要的作用，但功能失调的线粒体会导致细胞过程的扰动，最终导致细胞死亡。选择性去除和降解功能失调的线粒体的过程，线粒体自噬，防止异常线粒体的积累，因此在维持细胞健康方面具有保护作用。越来越多的研究将有缺陷的线粒体自噬与一系列疾病联系起来，包括帕金森病 (PD)。虽然目前的 PD 治疗策略可以改善该疾病的经典运动症状，但它们也常常伴随着严重的副作用，并且通常无法解决该疾病中潜在的进行性神经变性。确定新的治疗目标，如线粒体自噬，因此，人们对 PD 研究越来越感兴趣。本综述将首先概述线粒体自噬的过程，然后在检查单基因和散发形式的 PD 中涉及线粒体自噬的证据之前，绘制线粒体自噬与更广泛的病理过程（如蛋白质积累和神经炎症）之间的联系。最后，本综述将检查迄今为止用于促进线粒体自噬的各种策略，讨论这些研究中产生的考虑因素，并提出一个框架，用于最终评估促进线粒体自噬的化合物及其作为 PD 患者治疗策略的可行性。在线粒体自噬与更广泛的病理过程（如蛋白质积累和神经炎症）之间建立联系。最后，本综述将检查迄今为止用于促进线粒体自噬的各种策略，讨论这些研究中产生的考虑因素，并提出一个框架，用于最终评估促进线粒体自噬的化合物及其作为 PD 患者治疗策略的可行性。在线粒体自噬与更广泛的病理过程（如蛋白质积累和神经炎症）之间建立联系。最后，本综述将检查迄今为止用于促进线粒体自噬的各种策略，讨论这些研究中产生的考虑因素，并提出一个框架，用于最终评估促进线粒体自噬的化合物及其作为 PD 患者治疗策略的可行性。