ER stress: can the liver cope?

Hepatocytes contain abundant endoplasmic reticulum (ER) which is essential for protein metabolism and stress signaling. Hepatic viral infections, metabolic disorders, mutations of genes encoding ER-resident proteins, and abuse of alcohol or drugs can induce ER stress. Liver cells cope with ER stress by an adaptive protective response termed unfolded protein response (UPR), which includes enhancing protein folding and degradation in the ER and down-regulating overall protein synthesis. When the UPR adaptation to ER stress is insufficient, the ER stress response unleashes pathological consequences including hepatic fat accumulation, inflammation and cell death which can lead to liver disease or worsen underlying causes of liver injury, such as viral or diabetes-obesity-related liver disease.