scholarly journals ERO1α-dependent endoplasmic reticulum–mitochondrial calcium flux contributes to ER stress and mitochondrial permeabilization by procaspase-activating compound-1 (PAC-1)

2013 ◽  
Vol 4 (12) ◽  
pp. e968-e968 ◽  
Author(s):  
M Seervi ◽  
P K Sobhan ◽  
J Joseph ◽  
K Ann Mathew ◽  
T R Santhoshkumar
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Calcium Flux ◽  
Mitochondrial Calcium ◽  
Mitochondrial Permeabilization

scholarly journals ER–Mitochondria contact sites: A new regulator of cellular calcium flux comes into play

2016 ◽  
Vol 214 (4) ◽  
pp. 367-370 ◽  
Author(s):  
Michiel Krols ◽  
Geert Bultynck ◽  
Sophie Janssens
Keyword(s):  
Endoplasmic Reticulum ◽  
Calcium Signaling ◽  
Calcium Pump ◽  
Calcium Flux ◽  
Mitochondrial Calcium ◽  
Mitochondrial Bioenergetics ◽  
Cellular Calcium ◽  
Contact Sites ◽  
Cell Biol ◽  
Membrane Contacts

Endoplasmic reticulum (ER)–mitochondria membrane contacts are hotspots for calcium signaling. In this issue, Raturi et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201512077) show that the thioredoxin TMX1 inhibits the calcium pump SERCA2b at ER–mitochondria contact sites, thereby affecting ER–mitochondrial calcium transfer and mitochondrial bioenergetics.

scholarly journals LncRNA-DRSGN (Down-Regulated in Spiral Ganglion Neurons) Competes with miR-27a for Binding to FAM172A, Supervises SGN Degeneration and ER (Endoplasmic Reticulum) Stress-Autophagy in CHARGE Syndrome

2021 ◽  
Author(s):  
Xian-Bao Cao ◽  
Bi-Zhang Lu ◽  
Jia-Hong Pei ◽  
Cun Feng ◽  
Yan-Fei Guan ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Current Model ◽  
Spiral Ganglion ◽  
Noncoding Rnas ◽  
Charge Syndrome ◽  
Calcium Flux ◽  
Knockout Mouse Model ◽  
Ganglion Neurons

Abstract Background: Hearing loss is one of the most common disabilities in the world and brings a heavy burden to society. The current model is not stable enough, and it has caused serious model interference to clarify the pathogenesis of CHARGE syndrome. Methods: The knockout mouse model of FAM172A gene was constructed, and sits phenotype was identified. Besides, the next-genesequencing experiments of noncoding RNAs were performed utilizing the primary SGNs of model mice. The biofunctions of FAM172A in the relationships between ER (Endoplasmic reticulum) stress, autophagy, and intracellular calcium flux were investigated. Moreover, the above role associated with the competitive combination among LncRNA-DRSGN, miR-27a, and FAM172A were studied in the progression of SGN degeneration and autophagy in the model of CHARGE syndrome. Results: FAM172A(-/-) exhibited abnormal hearing, growth retardation, abnormal eye development, and dysgnosia. It was in line with the phenotype of CHARGE syndrome. Moreover, there was degeneration of SGNs in FAM172A(-/-) mice, and the differential expression of noncoding RNAs in primary SGNs were found and identified, including miR-27a and LncRNA-DRSGN. LncRNA-DRSGN regulated miR-27a as a ceRNA, and miR-27a inhibited FAM172A expression, LncRNA-DRSGN competed with miR-27a for binding to FAM172A, which participated in the regulation of ER stress-related calcium flux. LncRNA-DRSGN regulated the autophagy process of neurons by competing with miR-27a for binding to FAM172A. Conclusion: LncRNA-DRSGN competed with miR-27a for binding to FAM172A, participated in regulating ER stress-related calcium flux, then affected neuron degeneration and autophagy process of SGNs in the model of CHARGE syndrome.

scholarly journals Caspase-2 Cleavage of BID Is a Critical Apoptotic Signal Downstream of Endoplasmic Reticulum Stress

2008 ◽  
Vol 28 (12) ◽  
pp. 3943-3951 ◽  
Author(s):  
John-Paul Upton ◽  
Kathryn Austgen ◽  
Mari Nishino ◽  
Kristen M. Coakley ◽  
Andrew Hagen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cell Loss ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Proteolytic Activation ◽  
Caspase 2 ◽  
Induced Apoptosis ◽  
Mitochondrial Permeabilization ◽  
Apoptotic Signal

ABSTRACT The accumulation of misfolded proteins stresses the endoplasmic reticulum (ER) and triggers cell death through activation of the multidomain proapoptotic BCL-2 proteins BAX and BAK at the outer mitochondrial membrane. The signaling events that connect ER stress with the mitochondrial apoptotic machinery remain unclear, despite evidence that deregulation of this pathway contributes to cell loss in many human degenerative diseases. In order to “trap” and identify the apoptotic signals upstream of mitochondrial permeabilization, we challenged Bax − / − Bak − / − mouse embryonic fibroblasts with pharmacological inducers of ER stress. We found that ER stress induces proteolytic activation of the BH3-only protein BID as a critical apoptotic switch. Moreover, we identified caspase-2 as the premitochondrial protease that cleaves BID in response to ER stress and showed that resistance to ER stress-induced apoptosis can be conferred by inhibiting caspase-2 activity. Our work defines a novel signaling pathway that couples the ER and mitochondria and establishes a principal apoptotic effector downstream of ER stress.

scholarly journals The Endoplasmic Reticulum pool of Bcl-xL dampens the Unfolded Protein Response through IP3R-dependent Calcium Release

2021 ◽  
Author(s):  
Lea Jabbour ◽  
Trang Nguyen ◽  
Rudy Gadet ◽  
Olivier Lohez ◽  
Ivan Mikaelian ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Calcium Release ◽  
Calcium Flux ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Er Calcium

AbstractApoptosis plays a role in cell homeostasis in both normal development and disease. Bcl-xL, a member of the Bcl-2 family of proteins, regulates the intrinsic mitochondrial pathway of apoptosis. It is overexpressed in several cancers. Bcl-xL has a dual subcellular localization and is found at the mitochondria as well as the endoplasmic reticulum (ER). However, the biological significance of its ER localization is unclear. In order to decipher the functional contributions of the mitochondrial and reticular pools of Bcl-xL, we generated genetically modified mice expressing exclusively Bcl-xL at the ER, referred to as ER-xL, or the mitochondria, referred to as Mt-xL. By performing cell death assays, we showed that ER-xL MEFs show increased vulnerability to apoptotic stimuli but are more resistant to ER stress. Furthermore, ER-xL MEFs demonstrated a reduced expression of the Unfolded Protein Response (UPR) markers upon ER stress and displayed reduced inositol trisphosphate receptor (IP3R)-mediated ER calcium release. Collectively, our data show that upon ER stress, Bcl-xL negatively regulates IP3R-mediated calcium flux from the ER, which prevents ER calcium depletion and maintains the UPR and subsequent cell death in check. This work reveals a moonlighting function of Bcl-xL at the ER, apart from its cliché regulation of apoptosis.

Inhibition of Autophagy Potentiated Hippocampal Cell Death Induced by Endoplasmic Reticulum Stress and its Activation by Trehalose Failed to be Neuroprotective

2019 ◽  
Vol 16 (1) ◽  
pp. 3-11
Author(s):  
Luisa Halbe ◽  
Abdelhaq Rami
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Cell Damage ◽  
Protective Mechanism ◽  
Unfolded Proteins ◽  
Neuronal Viability ◽  
Hippocampal Cell ◽  
Trigger Cell Death ◽  
Autophagy Inhibition

Introduction: Endoplasmic reticulum (ER) stress induced the mobilization of two protein breakdown routes, the proteasomal- and autophagy-associated degradation. During ERassociated degradation, unfolded ER proteins are translocated to the cytosol where they are cleaved by the proteasome. When the accumulation of misfolded or unfolded proteins excels the ER capacity, autophagy can be activated in order to undertake the degradative machinery and to attenuate the ER stress. Autophagy is a mechanism by which macromolecules and defective organelles are included in autophagosomes and delivered to lysosomes for degradation and recycling of bioenergetics substrate. Materials and Methods: Autophagy upon ER stress serves initially as a protective mechanism, however when the stress is more pronounced the autophagic response will trigger cell death. Because autophagy could function as a double edged sword in cell viability, we examined the effects autophagy modulation on ER stress-induced cell death in HT22 murine hippocampal neuronal cells. We investigated the effects of both autophagy-inhibition by 3-methyladenine (3-MA) and autophagy-activation by trehalose on ER-stress induced damage in hippocampal HT22 neurons. We evaluated the expression of ER stress- and autophagy-sensors as well as the neuronal viability. Results and Conclusion: Based on our findings, we conclude that under ER-stress conditions, inhibition of autophagy exacerbates cell damage and induction of autophagy by trehalose failed to be neuroprotective.

Testicular Injury Attenuated by Rapamycin Through Induction of Autophagy and Inhibition of Endoplasmic Reticulum Stress in Streptozotocin- Induced Diabetic Rats

2019 ◽  
Vol 19 (5) ◽  
pp. 665-675 ◽  
Author(s):  
Wenjiao Shi ◽  
Zhixin Guo ◽  
Ruixia Yuan
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protective Effect ◽  
Er Stress ◽  
B Cell Lymphoma ◽  
Diabetic Rats ◽  
Pathological Changes ◽  
Rapamycin Treatment ◽  
Related Proteins

Background and Objective: This study investigated whether rapamycin has a protective effect on the testis of diabetic rats by regulating autophagy, endoplasmic reticulum stress, and oxidative stress. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups: control, diabetic, and diabetic treated with rapamycin, which received gavage of rapamycin (2mg.kg-1.d-1) after induction of diabetes. Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 65mg.Kg-1). All rats were sacrificed at the termination after 8 weeks of rapamycin treatment. The testicular pathological changes were determined by hematoxylin and eosin staining. The protein or mRNA expression of autophagy-related proteins (Beclin1, microtubule-associated protein light chain 3 (LC3), p62), ER stress marked proteins (CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), caspase-12), oxidative stress-related proteins (p22phox, nuclear factor erythroid2-related factor 2 (Nrf2)) and apoptosis-related proteins (Bax, B cell lymphoma-2 (Bcl-2)) were assayed by western blot or real-time fluorescence quantitative PCR. Results: There were significant pathological changes in the testes of diabetic rats. The expression of Beclin1, LC3, Nrf2, Bcl-2 were significantly decreased and p62, CHOP, caspase12, p22phox, and Bax were notably increased in the testis of diabetic rats (P <0.05). However, rapamycin treatment for 8 weeks significantly reversed the above changes in the testis of diabetic rats (P <0.05). Conclusion: Rapamycin appears to produce a protective effect on the testes of diabetic rats by inducing the expression of autophagy and inhibiting the expression of ER-stress, oxidative stress, and apoptosis.

scholarly journals EGFRvIII Promotes Cell Survival during Endoplasmic Reticulum Stress through a Reticulocalbin 1-Dependent Mechanism

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1198
Author(s):  
Juliana Gomez ◽  
Zammam Areeb ◽  
Sarah F. Stuart ◽  
Hong P. T. Nguyen ◽  
Lucia Paradiso ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Viability ◽  
Er Stress ◽  
Cell Survival ◽  
Glioblastoma Cells ◽  
Over Expression ◽  
Stress Markers ◽  
Apoptotic Protein ◽  
Novel Association ◽  
Reduced Activity

Reticulocalbin 1 (RCN1) is an endoplasmic reticulum (ER)-residing protein, involved in promoting cell survival during pathophysiological conditions that lead to ER stress. However, the key upstream receptor tyrosine kinase that regulates RCN1 expression and its potential role in cell survival in the glioblastoma setting have not been determined. Here, we demonstrate that RCN1 expression significantly correlates with poor glioblastoma patient survival. We also demonstrate that glioblastoma cells with expression of EGFRvIII receptor also have high RCN1 expression. Over-expression of wildtype EGFR also correlated with high RCN1 expression, suggesting that EGFR and EGFRvIII regulate RCN1 expression. Importantly, cells that expressed EGFRvIII and subsequently showed high RCN1 expression displayed greater cell viability under ER stress compared to EGFRvIII negative glioblastoma cells. Consistently, we also demonstrated that RCN1 knockdown reduced cell viability and exogenous introduction of RCN1 enhanced cell viability following induction of ER stress. Mechanistically, we demonstrate that the EGFRvIII-RCN1-driven increase in cell survival is due to the inactivation of the ER stress markers ATF4 and ATF6, maintained expression of the anti-apoptotic protein Bcl-2 and reduced activity of caspase 3/7. Our current findings identify that EGFRvIII regulates RCN1 expression and that this novel association promotes cell survival in glioblastoma cells during ER stress.

scholarly journals VDAC regulation of mitochondrial calcium flux: From channel biophysics to disease

Cell Calcium ◽  
2021 ◽  
Vol 94 ◽  
pp. 102356 ◽  
Author(s):  
William M. Rosencrans ◽  
Megha Rajendran ◽  
Sergey M. Bezrukov ◽  
Tatiana K. Rostovtseva
Keyword(s):  
Calcium Flux ◽  
Mitochondrial Calcium
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