Reduction of endoplasmic reticulum stress attenuates the defects caused by Drosophila mitofusin depletion

Ablation of the mitochondrial fusion and endoplasmic reticulum (ER)–tethering protein Mfn2 causes ER stress, but whether this is just an epiphenomenon of mitochondrial dysfunction or a contributor to the phenotypes in mitofusin (Mfn)-depleted Drosophila melanogaster is unclear. In this paper, we show that reduction of ER dysfunction ameliorates the functional and developmental defects of flies lacking the single Mfn mitochondrial assembly regulatory factor (Marf). Ubiquitous or neuron- and muscle-specific Marf ablation was lethal, altering mitochondrial and ER morphology and triggering ER stress that was conversely absent in flies lacking the fusion protein optic atrophy 1. Expression of Mfn2 and ER stress reduction in flies lacking Marf corrected ER shape, attenuating the developmental and motor defects. Thus, ER stress is a targetable pathogenetic component of the phenotypes caused by Drosophila Mfn ablation.

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Sophorolipid exhibits antifungal activity by ROS mediated endoplasmic reticulum stress and mitochondrial dysfunction pathways in Candida albicans

RSC Advances ◽

10.1039/c9ra07599b ◽

2019 ◽

Vol 9 (71) ◽

pp. 41639-41648 ◽

Cited By ~ 3

Author(s):

Farazul Haque ◽

Nitish Kumar Verma ◽

Mohammad Alfatah ◽

Swati Bijlani ◽

Mani Shankar Bhattacharyya

Keyword(s):

Endoplasmic Reticulum ◽

Cell Death ◽

Candida Albicans ◽

Antifungal Activity ◽

Endoplasmic Reticulum Stress ◽

Er Stress ◽

Mitochondrial Dysfunction ◽

Ros Generation

Sophorolipid induces ROS generation in C. albicans leading to mitochondrial dysfunction and ER stress followed by the release of Ca2+ ions (from the ER lumen) that enter mitochondria and further magnify ROS generation leading to cell death.

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Overexpression of calreticulin fails to abolish its induction by perturbation of normal ER function

Biochemistry and Cell Biology ◽

10.1139/o98-073 ◽

1998 ◽

Vol 76 (5) ◽

pp. 875-880 ◽

Cited By ~ 7

Author(s):

David H Llewellyn ◽

H Llewelyn Roderick

Keyword(s):

Endoplasmic Reticulum ◽

Stress Response ◽

Endoplasmic Reticulum Stress ◽

Fusion Protein ◽

Er Stress ◽

Hela Cells ◽

Mammalian Cells ◽

Stress Signaling ◽

Glucose Response ◽

The Stability

Along with other endoplasmic reticulum (ER) Ca2+-binding proteins, notably the glucose-response proteins grp78 and grp94, expression of calreticulin is induced in response to perturbation of normal ER function. It has yet to be clearly defined how this stress is signaled from the ER to the nucleus in mammalian cells, particularly with regard to its initiation. Using a GFP-calreticulin fusion protein, we have generated and selected stably transfected HeLa cells that overexpress calreticulin to investigate whether the protein might be involved in signaling its own induction. Basal levels of endogenous calreticulin mRNA and protein were unaffected in these cells, indicating that overexpression alone does not induce a stress response. ER stress induced calreticulin expression in response to either thapsigargin or tunicamycin was equivalent in these cells to that seen in control, nontransfected cells, leading us to conclude that calreticulin is unlikely be involved in its own induction. Levels of the mRNA encoding the fusion protein were also increased by tunicamycin, but not thapsigargin, suggesting that, in agreement with our previous observations, inhibition of N-linked glycosylation may increase the stability of calreticulin mRNA. This indicates that in mammalian cells, there is more than one signaling pathway for the ER stress response.Key words: calreticulin, endoplasmic reticulum stress, signaling.

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Mito-TEMPO Alleviates Renal Fibrosis by Reducing Inflammation, Mitochondrial Dysfunction, and Endoplasmic Reticulum Stress

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/5828120 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 14

Author(s):

Yuqing Liu ◽

Yundan Wang ◽

Wei Ding ◽

Yingdeng Wang

Keyword(s):

Oxidative Stress ◽

Chronic Kidney Disease ◽

Endoplasmic Reticulum ◽

Kidney Disease ◽

Endoplasmic Reticulum Stress ◽

Er Stress ◽

Mitochondrial Dysfunction ◽

Renal Fibrosis ◽

Oxidative Stress Markers ◽

Stress Markers

Background. Renal fibrosis is a common pathological symptom of chronic kidney disease (CKD). Many studies support that mitochondrial dysfunction and endoplasmic reticulum (ER) stress are implicated in the pathogenesis of CKD. In our study, we investigated the benefits and underlying mechanisms of Mito-TEMPO on renal fibrosis in 5/6 nephrectomy mice. Methods. Mice were randomly divided into five groups as follows: control group, CKD group, CKD + Mito-TEMPO (1 mg·kg−1·day−1) group, CKD + Mito-TEMPO (3 mg·kg−1·day−1) group, and Mito-TEMPO group (3 mg·kg−1·day−1). Renal fibrosis was evaluated by PAS, Masson staining, immunohistochemistry, and real-time PCR. Oxidative stress markers such as SOD2 activity and MDA level in serum and isolated mitochondria from renal tissue were measured by assay kits. Mitochondrial superoxide production was evaluated by MitoSOX staining and Western blot. Mitochondrial dysfunction was assessed by electron microscopy and real-time PCR. ER stress-associated protein was measured by Western blot. Results. Impaired renal function and renal fibrosis were significantly improved by Mito-TEMPO treatment. Furthermore, inflammation cytokines, profibrotic factors, oxidative stress markers, mitochondrial dysfunction, and ER stress were all increased in the CKD group. However, these effects were significantly ameliorated in the Mito-TEMPO treatment group. Conclusions. Mito-TEMPO ameliorates renal fibrosis by alleviating mitochondrial dysfunction and endoplasmic reticulum stress possibly through the Sirt3-SOD2 pathway, which sheds new light on prevention of renal fibrosis in chronic kidney disease.

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

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666190102112844 ◽

2019 ◽

Vol 19 (5) ◽

pp. 665-675 ◽

Cited By ~ 4

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.

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Different Expression of Mitochondrial and Endoplasmic Reticulum Stress Genes in Epicardial Adipose Tissue Depends on Coronary Atherosclerosis

International Journal of Molecular Sciences ◽

10.3390/ijms22094538 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4538

Author(s):

Helena Kratochvílová ◽

Miloš Mráz ◽

Barbora J. Kasperová ◽

Daniel Hlaváček ◽

Jakub Mahrík ◽

...

Keyword(s):

Skeletal Muscle ◽

Endoplasmic Reticulum ◽

Adipose Tissue ◽

Cardiac Surgery ◽

Endoplasmic Reticulum Stress ◽

Er Stress ◽

Mrna Expression ◽

Coronary Atherosclerosis ◽

Stress Genes ◽

Valvular Surgery

The aim of our study was to analyze mitochondrial and endoplasmic reticulum (ER) gene expression profiles in subcutaneous (SAT) and epicardial (EAT) adipose tissue, skeletal muscle, and myocardium in patients with and without CAD undergoing elective cardiac surgery. Thirty-eight patients, 27 with (CAD group) and 11 without CAD (noCAD group), undergoing coronary artery bypass grafting and/or valvular surgery were included in the study. EAT, SAT, intercostal skeletal muscle, and right atrium tissue and blood samples were collected at the start and end of surgery; mRNA expression of selected mitochondrial and ER stress genes was assessed using qRT-PCR. The presence of CAD was associated with decreased mRNA expression of most of the investigated mitochondrial respiratory chain genes in EAT, while no such changes were seen in SAT or other tissues. In contrast, the expression of ER stress genes did not differ between the CAD and noCAD groups in almost any tissue. Cardiac surgery further augmented mitochondrial dysfunction in EAT. In our study, CAD was associated with decreased expression of mitochondrial, but not endoplasmic reticulum stress genes in EAT. These changes may contribute to the acceleration of coronary atherosclerosis.

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Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

International Journal of Molecular Sciences ◽

10.3390/ijms22094646 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4646

Author(s):

Alexey A. Tinkov ◽

Monica M. B. Paoliello ◽

Aksana N. Mazilina ◽

Anatoly V. Skalny ◽

Airton C. Martins ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Mitochondrial Dysfunction ◽

Synaptic Dysfunction ◽

Future Research ◽

Protective Mechanism ◽

Autophagic Flux ◽

Future Research Directions ◽

The Impact

Understanding of the immediate mechanisms of Mn-induced neurotoxicity is rapidly evolving. We seek to provide a summary of recent findings in the field, with an emphasis to clarify existing gaps and future research directions. We provide, here, a brief review of pertinent discoveries related to Mn-induced neurotoxicity research from the last five years. Significant progress was achieved in understanding the role of Mn transporters, such as SLC39A14, SLC39A8, and SLC30A10, in the regulation of systemic and brain manganese handling. Genetic analysis identified multiple metabolic pathways that could be considered as Mn neurotoxicity targets, including oxidative stress, endoplasmic reticulum stress, apoptosis, neuroinflammation, cell signaling pathways, and interference with neurotransmitter metabolism, to name a few. Recent findings have also demonstrated the impact of Mn exposure on transcriptional regulation of these pathways. There is a significant role of autophagy as a protective mechanism against cytotoxic Mn neurotoxicity, yet also a role for Mn to induce autophagic flux itself and autophagic dysfunction under conditions of decreased Mn bioavailability. This ambivalent role may be at the crossroad of mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis. Yet very recent evidence suggests Mn can have toxic impacts below the no observed adverse effect of Mn-induced mitochondrial dysfunction. The impact of Mn exposure on supramolecular complexes SNARE and NLRP3 inflammasome greatly contributes to Mn-induced synaptic dysfunction and neuroinflammation, respectively. The aforementioned effects might be at least partially mediated by the impact of Mn on α-synuclein accumulation. In addition to Mn-induced synaptic dysfunction, impaired neurotransmission is shown to be mediated by the effects of Mn on neurotransmitter systems and their complex interplay. Although multiple novel mechanisms have been highlighted, additional studies are required to identify the critical targets of Mn-induced neurotoxicity.

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Catechin-7-O-xyloside induces apoptosis via endoplasmic reticulum stress and mitochondrial dysfunction in human non-small cell lung carcinoma H1299 cells

Oncology Reports ◽

10.3892/or.2013.2840 ◽

2013 ◽

Vol 31 (1) ◽

pp. 314-320 ◽

Cited By ~ 3

Author(s):

JANG WON YOON ◽

JONG SUK LEE ◽

BYEONG MO KIM ◽

JOUNGJWA AHN ◽

KYUNG MI YANG

Keyword(s):

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Mitochondrial Dysfunction ◽

Lung Carcinoma ◽

Small Cell Lung Carcinoma ◽

Small Cell ◽

Small Cell Lung ◽

Cell Lung Carcinoma

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The impact of obesity on oocytes: evidence for lipotoxicity mechanisms

Reproduction Fertility and Development ◽

10.1071/rd11904 ◽

2012 ◽

Vol 24 (1) ◽

pp. 29 ◽

Cited By ~ 31

Author(s):

Linda L.-Y. Wu ◽

Robert J. Norman ◽

Rebecca L. Robker

Keyword(s):

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Mitochondrial Dysfunction ◽

Intracytoplasmic Sperm Injection ◽

Oocyte Quality ◽

Early Embryo ◽

Pregnancy Rates ◽

Clinical Literature ◽

The Impact

Obesity can have detrimental effects on pregnancy rates in natural conceptions and also in women undergoing IVF or intracytoplasmic sperm injection (ICSI). This review summarises the most recent clinical literature investigating whether obesity impacts oocyte quality and early embryo growth. In other tissues, obesity leads to lipotoxicity responses including endoplasmic reticulum stress, mitochondrial dysfunction and apoptosis. Recent reports indicate that lipotoxicity is a mechanism by which obesity may impact oocyte quality.

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