Kang Zhanfang, Chen Feng, Wu Wanhui, Liu Rui, Chen Tianda, Xu Fang
Department of Basic Medical Research, Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, China.
Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
Front Cell Dev Biol. 2022 Sep 16;10:974083. doi: 10.3389/fcell.2022.974083. eCollection 2022.
The mitochondrial unfolded protein response (UPR) is a molecular mechanism that maintains mitochondrial proteostasis under stress and is closely related to various metabolic diseases, such as type 2 diabetes (T2D). Similarly, the unfolded protein response of the endoplasmic reticulum (UPR) is responsible for maintaining proteomic stability in the endoplasmic reticulum (ER). Since the mitochondria and endoplasmic reticulum are the primary centers of energy metabolism and protein synthesis in cells, respectively, a synergistic mechanism must exist between UPR and UPR to cooperatively resist stresses such as hyperglycemia in T2D. Increasing evidence suggests that the protein kinase RNA (PKR)-like endoplasmic reticulum kinase (PERK) signaling pathway is likely an important node for coordinating UPR and UPR. The PERK pathway is activated in both UPR and UPR, and its downstream molecules perform important functions. In this review, we discuss the mechanisms of UPR, UPR and their crosstalk in T2D.
线粒体未折叠蛋白反应（UPR）是一种在应激状态下维持线粒体蛋白质稳态的分子机制，与2型糖尿病（T2D）等多种代谢性疾病密切相关。同样，内质网未折叠蛋白反应（UPR）负责维持内质网（ER）中的蛋白质组稳定性。由于线粒体和内质网分别是细胞中能量代谢和蛋白质合成的主要中心，因此UPR和UPR之间必然存在一种协同机制，以协同抵抗T2D中的高血糖等应激。越来越多的证据表明，蛋白激酶RNA（PKR）样内质网激酶（PERK）信号通路可能是协调UPR和UPR的重要节点。PERK通路在UPR和UPR中均被激活，其下游分子发挥重要作用。在本综述中，我们讨论了UPR、UPR的机制及其在T2D中的相互作用。
