UPR^mt and coordinated UPR^ER in type 2 diabetes

The mitochondrial unfolded protein response (UPR^mt) 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^ER) 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^mt and UPR^ER 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^mt and UPR^ER. The PERK pathway is activated in both UPR^mt and UPR^ER, and its downstream molecules perform important functions. In this review, we discuss the mechanisms of UPR^mt, UPR^ER and their crosstalk in T2D.