Endoplasmic Reticulum Stress in the β-Cell Pathogenesis of Type 2 Diabetes

Figure 2

Potential activation mechanisms for disposing misfolded proteins from the ER. Misfolded proteins in the ER can be disposed of by serial activation of ERAD, pQC and autophagy according to the degree of protein misfolding and aggregation. In general, a small amount of protein is spontaneously misfolded and efficiently degraded in the ER even in the resting state. Under ER stress, accumulation of misfolded proteins in the ER activates pQC to reduce the burden of proteins in damaged ER as well as the ERAD pathway to dispose of misfolded proteins from the ER. However, under prolonged ER stress, ERAD does not efficiently dispose of and degrade protein aggregates from the ER, resulting in activation of an alternative way to clean them up from the ER, called “autophagy”. Activation of these pathways is aimed at increasing ER capacity for protecting cells from misfolded proteins.