ER Stress and Autophagy

Abstract

Eukaryotic cells respond to various types of stresses caused by changes in the extracellular environment. Intracellular factors, such as the accumulation of misfolded proteins in the endoplasmic reticulum (ER), also cause stress and activate the unfolded protein response (UPR), which induces the expression of chaperones and proteins involved in the recovery process. However, if the stress is excessive or sustained, and ER function cannot be restored, the UPR triggers apoptosis, thereby removing the affected cell. It is now apparent that ER stress is also a potent trigger for autophagy, a self-degradative process that has an adaptive function. This review surveys the intersection of ER stress and autophagy and highlights the potential therapeutic implications thereof.

High Glucose-Induced Podocyte Injury Involves Activation of Mammalian Target of Rapamycin (mTOR)-Induced Endoplasmic Reticulum (ER) Stress

“…Over-activated or prolonged ER stress can initiate apoptosis through two principal UPR receptors IRE-1 and PERK [16, 17]. In HG-treated podocytes, we found that the level of CHOP, Grp78 and the phosphorylated PERK at Thr389 was highly enhanced compared to NG- and MN-treated cells (Fig.…”

“…ER stress is also named as unfolded protein response (UPR) since it mainly deal with unfolded and/or miss-folded proteins [16, 17]. In the conditions of over-activated and/or prolonged ER stress, the role of UPR changes from promoting cellular survival to committing the cell to an apoptotic pathway.…”

“…In addition, inflammatory pathways may be involved in podocyte loss in DN [15]. Notably, endoplasmic reticulum (ER) stress is an important cellular response that is required for process of unfolded and/or misfolded proteins in cell [16]. Over-activated or prolonged ER stress may initiate cellular apoptosis through two principal unfolded protein response (UPR) receptors inositol-requiring enzyme (IRE-1) and protein kinase RNA-like ER kinase (PERK) [16, 17].…”

“…Notably, endoplasmic reticulum (ER) stress is an important cellular response that is required for process of unfolded and/or misfolded proteins in cell [16]. Over-activated or prolonged ER stress may initiate cellular apoptosis through two principal unfolded protein response (UPR) receptors inositol-requiring enzyme (IRE-1) and protein kinase RNA-like ER kinase (PERK) [16, 17]. It was reported that oxidative stress and ER stress pathways participate in Aldo-induced podocyte injury [18].…”

Autophagy-mediated catabolism of visual transduction proteins prevents retinal degeneration

“…Autophagy is particularly important in postmitotic cells where it functions to remove damaged components that would otherwise accumulate and harm the cell. 20,21 This concept has been borne out in numerous model systems, and dysfunctional autophagy has been implicated in neurodegenerative diseases such as Alzheimer and Huntington diseases. [22][23][24] In rod photoreceptors the light-/dark-induced translocation of phototransduction proteins is thought to regulate light sensitivity whereby the concentration of transducin and ARR/arrestin in the photoreceptor OS is the critical factor.…”