Open Access

The endoplasmic reticulum (ER) is a major cellular organelle consisting of a vast reticular network spanning from the nuclear envelope to the plasma membrane. It plays a major role in various cellular processes including protein synthesis and glycosylation, the secretory pathway, and membrane biogenesis. It is sensitive to changes in its lumenal homeostasis. Loss of ER lumenal homeostasis leads to a condition referred to as ER stress. The cellular response to ER stress is to orchestrate the activation of an evolutionarily conserved transcriptional program termed the unfolded protein response (UPR). A consequence of UPR is upregulation of the components of the autophagic machinery and increased autophagic flux. Over the past decade much research investigating the onset and progression of autophagy following activation of the UPR has been carried out. Owing to this we now have a better understanding of the signaling pathways leading to ER stress-mediated autophagy and have begun to appreciate the importance of the ER localized stress sensors, IRE1, ATF6, and PERK in this process. In this chapter we provide an overview of the current thinking concerning the role of ER stress and UPR in initiation and regulation of autophagy.