Center of Molecular and Translational Medicine, Institution of Biomedical Science, Georgia State University, Atlanta, GA 30303, USA.
Int J Mol Sci. 2020 May 28;21(11):3842. doi: 10.3390/ijms21113842.
Endoplasmic reticulum (ER) and mitochondrion are the key organelles in mammal cells and play crucial roles in a variety of biological functions in both physiological and pathological conditions. Valosin-containing protein VCP), a newly identified calcium-associated ATPase protein, has been found to be involved in both ER and mitochondrial function. Impairment of VCP, caused by structural mutations or alterations of expressions, contributes to the development of various diseases, through an integrating effect on ER, mitochondria and the ubiquitin-proteasome system, by interfering with protein degradation, subcellular translocation and calcium homeostasis. Thus, understanding the role and the molecular mechanisms of VCP in these organelles brings new insights to the pathogenesis of the associated diseases, and leads to the discovery of new therapeutic strategies. In this review, we summarized the progress of studies on VCP, in terms of its regulation of ER and mitochondrial function and its implications for the associated diseases, focusing on the cancers, heart disease, and neurodegenerative disorders.
内质网（ER）和线粒体是哺乳动物细胞中的关键细胞器，在生理和病理条件下的多种生物学功能中发挥着关键作用。包含 valosin 的蛋白（VCP）是一种新发现的钙相关 ATP 酶蛋白，已被发现参与 ER 和线粒体功能。VCP 的结构突变或表达改变导致其功能受损，通过干扰蛋白质降解、亚细胞易位和钙稳态，对 ER、线粒体和泛素-蛋白酶体系统产生综合影响，从而导致各种疾病的发生。因此，了解 VCP 在这些细胞器中的作用和分子机制，为相关疾病的发病机制提供了新的见解，并为发现新的治疗策略提供了依据。在这篇综述中，我们总结了 VCP 在调节 ER 和线粒体功能及其与相关疾病（特别是癌症、心脏病和神经退行性疾病）关系方面的研究进展，重点介绍了这方面的研究进展。
