Parkinson's disease (PD) is one of the most common neurodegenerative movement disorder characterized by preferential loss of dopaminergic neurons of the substantia nigra pars compacta and the presence of Lewy bodies containing α-synuclein. Although the cause of PD remains elusive, remarkable advances have been made in understanding the possible causative mechanisms of PD pathogenesis. An explosion of discoveries during the past two decades has led to the identification of several autosomal dominant and recessive genes that cause familial forms of PD. The investigations of these familial PD gene products have shed considerable insights into the molecular pathogenesis of the more common sporadic PD. A growing body of evidence suggests that the etiology of PD is multifactorial and involves a complex interplay between genetic and environmental factors. Substantial evidence from human tissues, genetic and toxin-induced animal and cellular models indicates that mitochondrial dysfunction plays a central role in the pathophysiology of PD. Deficits in mitochondrial functions due to bioenergetics defects, alterations in the mitochondrial DNA, generation of reactive oxygen species, aberrant calcium homeostasis, and anomalies in mitochondrial dynamics and quality control are implicated in the underlying mechanisms of neuronal cell death in PD. In this review, we discuss how familial PD-linked genes and environmental factors interface the pathways regulating mitochondrial functions and thereby potentially converge both familial and sporadic PD at the level of mitochondrial integrity. We also provide an overview of the status of therapeutic strategies targeting mitochondrial dysfunction in PD. Unraveling potential pathways that influence mitochondrial homeostasis in PD may hold the key to therapeutic intervention for this debilitating neurodegenerative movement disorder.

帕金森氏病（PD）是最常见的神经退行性运动障碍之一，其特征是黑质致密部的多巴胺能神经元优先丢失以及含有α-突触核蛋白的路易体的存在。尽管PD的病因尚不清楚，但是在了解PD发病机理的可能病因机制方面已经取得了显着进展。在过去的二十年里，发现的爆炸式增长导致鉴定出了几种常染色体显性遗传基因和隐性基因，这些基因导致了家族性的PD。对这些家族性PD基因产物的研究为更常见的散发性PD的分子发病机理提供了可观的见解。越来越多的证据表明，PD的病因是多因素的，并且涉及遗传和环境因素之间的复杂相互作用。来自人体组织，遗传和毒素诱导的动物和细胞模型的大量证据表明，线粒体功能障碍在PD的病理生理中起着重要作用。由于PD的神经元细胞死亡的潜在机制，归因于生物能缺陷，线粒体DNA的改变，活性氧种类的产生，钙稳态的异常以及线粒体动力学和质量控制的异常，从而导致线粒体功能的缺陷。在这篇评论中，我们讨论了家族性PD相关基因和环境因子如何介导调节线粒体功能的途径，从而潜在地将家族性和散发性PD融合在线粒体完整性水平上。我们还概述了针对PD中线粒体功能障碍的治疗策略的现状。揭示影响PD中线粒体体内稳态的潜在途径可能是这种令人衰弱的神经退行性运动障碍治疗干预的关键。