Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, Hunan, China.
Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, Hunan, China.
Pharmacol Res. 2020 Oct;160:105080. doi: 10.1016/j.phrs.2020.105080. Epub 2020 Jul 13.
Mitochondria-associated membranes (MAMs) are the organellar contact sites between mitochondria and the endoplasmic reticulum (ER), and recent studies demonstrated that MAMs, which serve as multiple scaffolds of proteins, are involved in Ca signaling, lipid metabolism, mitochondrial morphology and functions, and autophagy. Importantly, several pathological conditions, such as obesity, diabetes mellitus and neurodegenerative diseases, indicate the significant role of MAMs in cellular homeostasis. Phosphofurin acidic cluster sorting protein 2(PACS-2), a multifunctional sorting protein at MAMs, plays a critical role in mitochondria, ER and lysosome homeostasis. In this review, we summarize the current understanding of the role of PACS-2 as a key regulator of MAMs and present the structure and other functions of PACS-2. Moreover, we describe the relationship between PACS-2 and diseases to reveal its potential as a novel therapeutic target that can be applied for the treatment of diseases.
线粒体相关膜(MAMs)是线粒体和内质网(ER)之间的细胞器接触位点,最近的研究表明,MAMs 作为多种蛋白质支架,参与 Ca 信号转导、脂质代谢、线粒体形态和功能以及自噬。重要的是,几种病理状况,如肥胖、糖尿病和神经退行性疾病,表明 MAMs 在细胞内稳态中具有重要作用。磷酸化富亮氨酸酸性簇分选蛋白 2(PACS-2),MAMs 上的一种多功能分选蛋白,在线粒体、内质网和溶酶体稳态中发挥着关键作用。在这篇综述中,我们总结了目前对 PACS-2 作为 MAMs 关键调节剂的作用的认识,并介绍了 PACS-2 的结构和其他功能。此外,我们描述了 PACS-2 与疾病之间的关系,以揭示其作为一种新的治疗靶点的潜力,可用于治疗疾病。