Mitochondrial dysfunction is a well-established pathological event in Parkinson’s disease (PD). Proteins misfolding and its impaired cellular clearance due to altered autophagy/mitophagy/pexophagy contribute to PD progression. It has been shown that mitochondria have contact sites with endoplasmic reticulum (ER), peroxisomes and lysosomes that are involved in regulating various physiological processes. In pathological conditions, the crosstalk at the contact sites initiates alterations in intracellular vesicular transport, calcium homeostasis and causes activation of proteases, protein misfolding and impairment of autophagy. Apart from the well-reported molecular changes like mitochondrial dysfunction, impaired autophagy/mitophagy and oxidative stress in PD, here we have summarized the recent scientific reports to provide the mechanistic insights on the altered communications between ER, peroxisomes, and lysosomes at mitochondrial contact sites. Furthermore, the manuscript elaborates on the contributions of mitochondrial contact sites and organelles dysfunction to the pathogenesis of PD and suggests potential therapeutic targets.

线粒体功能障碍是帕金森病 (PD) 中公认的病理事件。由于自噬/线粒体自噬/自噬改变导致蛋白质错误折叠及其细胞清除受损，导致 PD 进展。研究表明，线粒体与内质网（ER）、过氧化物酶体和溶酶体有接触位点，参与调节各种生理过程。在病理条件下，接触位点的串扰会引发细胞内囊泡运输、钙稳态的改变，并导致蛋白酶激活、蛋白质错误折叠和自噬受损。除了帕金森病中线粒体功能障碍、自噬/线粒体自噬受损和氧化应激等广泛报道的分子变化外，我们还总结了最近的科学报告，以提供有关线粒体接触位点的内质网、过氧化物酶体和溶酶体之间通讯改变的机制见解。此外，该手稿详细阐述了线粒体接触位点和细胞器功能障碍对 PD 发病机制的贡献，并提出了潜在的治疗靶点。