EI24 promotes cell adaption to ER stress by coordinating IRE1 signaling and calcium homeostasis

EMBO Reports ◽  
2022 ◽  
Author(s):  
Yiwei Xu ◽  
Jie Chen ◽  
Jianguo Chen ◽  
Junlin Teng
Keyword(s):  
Er Stress ◽  
Calcium Homeostasis

Mitochondria-associated ER membranes in glucose homeostasis and insulin resistance

2020 ◽  
Vol 319 (6) ◽  
pp. E1053-E1060
Author(s):  
Logan K. Townsend ◽  
Henver S. Brunetta ◽  
Marcelo A. S. Mori
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Endoplasmic Reticulum ◽  
Adipose Tissue ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Glucose Homeostasis ◽  
Calcium Homeostasis ◽  
Adenine Nucleotides ◽  
Current Controversy

Obesity and insulin resistance (IR) are associated with endoplasmic reticulum (ER) stress and mitochondrial dysfunction in several tissues. Although for many years mitochondrial and ER function were studied separately, these organelles also connect to produce interdependent functions. Communication occurs at mitochondria-associated ER membranes (MAMs) and regulates lipid and calcium homeostasis, apoptosis, and the exchange of adenine nucleotides, among other things. Recent evidence suggests that MAMs contribute to organelle, cellular, and systemic metabolism. In obesity and IR models, metabolic tissues such as the liver, skeletal muscle, pancreas, and adipose tissue present alterations in MAM structure or function. The purpose of this mini review is to highlight the MAM disruptions that occur in each tissue during obesity and IR and its relationship with glucose homeostasis and IR. We also discuss the current controversy that surrounds MAMs’ role in the development of IR.

scholarly journals Organelle Stress and Crosstalk in Kidney Disease

Kidney360 ◽  
2020 ◽  
Vol 1 (10) ◽  
pp. 1155-1162
Author(s):  
Sho Hasegawa ◽  
Reiko Inagi
Keyword(s):  
Kidney Disease ◽  
Er Stress ◽  
Calcium Homeostasis ◽  
Stress Responses ◽  
Primary Cilia ◽  
Proximal Tubular Cells ◽  
Cellular Homeostasis ◽  
Tubular Cells ◽  
Progression Of Kidney Disease ◽  
Proximal Tubular

Organelles play important roles in maintaining cellular homeostasis. Organelle stress responses, especially in mitochondria, endoplasmic reticula (ER), and primary cilia, are deeply involved in kidney disease pathophysiology. Mitochondria are the center of energy production in most eukaryotic cells. Renal proximal tubular cells are highly energy demanding and abundant in mitochondria. Mitochondrial dysfunctions in association with energy metabolism alterations produce reactive oxygen species and promote inflammation in proximal tubular cells, resulting in progression of kidney disease. The ER play critical roles in controlling protein quality. Unfolded protein response (UPR) pathways are the adaptive response to ER stress for maintaining protein homeostasis. UPR pathway dysregulation under pathogenic ER stress often occurs in glomerular and tubulointerstitial cells and promotes progression of kidney disease. The primary cilia sense extracellular signals and maintain calcium homeostasis in cells. Dysfunction of the primary cilia in autosomal dominant polycystic kidney disease reduces the calcium concentration in proximal tubular cells, leading to increased cell proliferation and retention of cyst fluid. In recent years, the direct interaction at membrane contact sites has received increased attention in association with the development of imaging technologies. The part of the ER that is directly connected to mitochondria is termed the mitochondria-associated ER membrane (MAM), which regulates calcium homeostasis and phospholipid metabolism in cells. Disruption of MAM integrity collapses cellular homeostasis and leads to diseases such as diabetes and Alzheimer disease. This review summarizes recent research on organelle stress and crosstalk, and their involvement in kidney disease pathophysiology. In addition, potential treatment options that target organelle stress responses are discussed.

scholarly journals Reticulon Protein-1C: A New Hope in the Treatment of Different Neuronal Diseases

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Federica Di Sano ◽  
Mauro Piacentini
Keyword(s):  
Cell Death ◽  
Membrane Proteins ◽  
Neurodegenerative Diseases ◽  
Er Stress ◽  
Calcium Homeostasis ◽  
Neurodegenerative Disorders ◽  
Cellular Functions ◽  
Promising Target ◽  
Specific Proteins ◽  
Structure And Functions

Reticulons (RTNs) are a group of membrane proteins localized on the ER and known to regulate ER structure and functions. Several studies have suggested that RTNs are involved in different important cellular functions such as changes in calcium homeostasis, ER-stress-mediated cell death, and autophagy. RTNs have been demonstrated to exert a cancer specific proapoptotic function via the interaction or the modulation of specific proteins. Reticulons have also been implicated in different signaling pathways which are at the basis of the pathogenesis of several neurodegenerative diseases. In this paper we discuss the accumulating evidence identifying RTN-1C protein as a promising target in the treatment of different pathologies such as cancer or neurodegenerative disorders.

scholarly journals STING-mediated disruption of calcium homeostasis chronically activates ER stress and primes T cell death

2019 ◽  
Vol 216 (4) ◽  
pp. 867-883 ◽  
Author(s):  
Jianjun Wu ◽  
Yu-Ju Chen ◽  
Nicole Dobbs ◽  
Tomomi Sakai ◽  
Jen Liou ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Er Stress ◽  
Lung Disease ◽  
Calcium Homeostasis ◽  
Cell Receptor ◽  
Type I ◽  
T Cell Survival

STING gain-of-function mutations cause lung disease and T cell cytopenia through unknown mechanisms. Here, we found that these mutants induce chronic activation of ER stress and unfolded protein response (UPR), leading to T cell death by apoptosis in the StingN153S/+ mouse and in human T cells. Mechanistically, STING-N154S disrupts calcium homeostasis in T cells, thus intrinsically primes T cells to become hyperresponsive to T cell receptor signaling–induced ER stress and the UPR, leading to cell death. This intrinsic priming effect is mediated through a novel region of STING that we name “the UPR motif,” which is distinct from known domains required for type I IFN signaling. Pharmacological inhibition of ER stress prevented StingN153S/+ T cell death in vivo. By crossing StingN153S/+ to the OT-1 mouse, we fully restored CD8+ T cells and drastically ameliorated STING-associated lung disease. Together, our data uncover a critical IFN-independent function of STING that regulates calcium homeostasis, ER stress, and T cell survival.

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