scholarly journals Advances in ER-Phagy and Its Diseases Relevance

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2328
Author(s):  
Lingang He ◽  
Xuehong Qian ◽  
Yixian Cui
Keyword(s):  
Endoplasmic Reticulum ◽  
Neurodegenerative Disorders ◽  
Metabolic Diseases ◽  
Therapeutic Strategies ◽  
Selective Autophagy ◽  
Autophagic Degradation ◽  
Novel Therapeutic Strategies ◽  
The Relationship ◽  
Important Form ◽  
Catabolic Process

As an important form of selective autophagy in cells, ER-phagy (endoplasmic reticulum-selective autophagy), the autophagic degradation of endoplasmic reticulum (ER), degrades ER membranes and proteins to maintain cellular homeostasis. The relationship between ER-phagy and human diseases, including neurodegenerative disorders, cancer, and other metabolic diseases has been unveiled by extensive research in recent years. Starting with the catabolic process of ER-phagy and key mediators in this pathway, this paper reviews the advances in the mechanism of ER-phagy and its diseases relevance. We hope to provide some enlightenment for further study on ER-phagy and the development of novel therapeutic strategies for related diseases.

scholarly journals Autophagosome formation in relation to the endoplasmic reticulum

2020 ◽  
Vol 27 (1) ◽  
Author(s):  
Yo-hei Yamamoto ◽  
Takeshi Noda
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Protein ◽  
De Novo ◽  
Transmembrane Protein ◽  
Lipid Transfer ◽  
Membrane Structures ◽  
Autophagosome Formation ◽  
Selective Autophagy ◽  
The Relationship ◽  
Er Membrane

Abstract Autophagy is a process in which a myriad membrane structures called autophagosomes are formed de novo in a single cell, which deliver the engulfed substrates into lysosomes for degradation. The size of the autophagosomes is relatively uniform in non-selective autophagy and variable in selective autophagy. It has been recently established that autophagosome formation occurs near the endoplasmic reticulum (ER). In this review, we have discussed recent advances in the relationship between autophagosome formation and endoplasmic reticulum. Autophagosome formation occurs near the ER subdomain enriched with phospholipid synthesizing enzymes like phosphatidylinositol synthase (PIS)/CDP-diacylglycerol-inositol 3-phosphatidyltransferase (CDIPT) and choline/ethanolamine phosphotransferase 1 (CEPT1). Autophagy-related protein 2 (Atg2), which is involved in autophagosome formation has a lipid transfer capacity and is proposed to directly transfer the lipid molecules from the ER to form autophagosomes. Vacuole membrane protein 1 (VMP1) and transmembrane protein 41b (TMEM41b) are ER membrane proteins that are associated with the formation of the subdomain. Recently, we have reported that an uncharacterized ER membrane protein possessing the DNAJ domain, called ERdj8/DNAJC16, is associated with the regulation of the size of autophagosomes. The localization of ERdj8/DNAJC16 partially overlaps with the PIS-enriched ER subdomain, thereby implying its association with autophagosome size determination.

scholarly journals Neuroprotective Potential of GDF11: Myth or Reality?

2019 ◽  
Vol 20 (14) ◽  
pp. 3563 ◽  
Author(s):  
Luc Rochette ◽  
Gabriel Malka
Keyword(s):  
Neurodegenerative Diseases ◽  
Blood Plasma ◽  
Neurodegenerative Disorders ◽  
Brain Aging ◽  
Therapeutic Strategies ◽  
Blood Concentrations ◽  
Age Related ◽  
Novel Therapeutic Strategies ◽  
The Brain ◽  
Novel Therapeutic

In the brain, aging is accompanied by cellular and functional deficiencies that promote vulnerability to neurodegenerative disorders. In blood plasma from young and old animals, various factors such as growth differentiation factor 11 (GDF11), whose levels are elevated in young animals, have been identified. The blood concentrations of these factors appear to be inversely correlated with the age-related decline of neurogenesis. The identification of GDF11 as a “rejuvenating factor” opens up perspectives for the treatment of neurodegenerative diseases. As a pro-neurogenic and pro-angiogenic agent, GDF11 may constitute a basis for novel therapeutic strategies.

Obesity and asthma: lessons from animal models

2007 ◽  
Vol 102 (2) ◽  
pp. 516-528 ◽  
Author(s):  
Stephanie A. Shore
Keyword(s):  
Epidemiological Data ◽  
Therapeutic Strategies ◽  
Murine Models ◽  
Asthmatic Subject ◽  
Tnf Α ◽  
Mechanical Factors ◽  
Mechanistic Basis ◽  
Novel Therapeutic Strategies ◽  
The Relationship

Epidemiological data indicate that obesity is a risk factor for asthma. These data are supported by observations in several murine models of obesity. Ob/ob, db/db, and Cpefatmice each exhibit innate airway hyperresponsiveness, a characteristic feature of asthma. These mice also respond more vigorously to common asthma triggers, including ozone. Here we discuss the implications of these data with respect to several mechanisms proposed to explain the relationship between obesity and asthma: 1) common etiologies; 2) comorbidities; 3) mechanical factors; and 4) adipokines. We focus on the role of adipokines, especially TNF-α, IL-6, leptin, and adiponectin. Understanding the mechanistic basis for the relationship between obesity and asthma may lead to novel therapeutic strategies for treatment of the obese asthmatic subject.

scholarly journals Targeting Autophagy for Cancer Treatment and Tumor Chemosensitization

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1599 ◽  
Author(s):  
Marta Pérez-Hernández ◽  
Alain Arias ◽  
David Martínez-García ◽  
Ricardo Pérez-Tomás ◽  
Roberto Quesada ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Therapeutic Strategy ◽  
Nutrient Recycling ◽  
Clinical Results ◽  
Therapeutic Strategies ◽  
Combination Therapies ◽  
Novel Therapeutic Strategies ◽  
Cellular Components ◽  
Catabolic Process

Autophagy is a tightly regulated catabolic process that facilitates nutrient recycling from damaged organelles and other cellular components through lysosomal degradation. Deregulation of this process has been associated with the development of several pathophysiological processes, such as cancer and neurodegenerative diseases. In cancer, autophagy has opposing roles, being either cytoprotective or cytotoxic. Thus, deciphering the role of autophagy in each tumor context is crucial. Moreover, autophagy has been shown to contribute to chemoresistance in some patients. In this regard, autophagy modulation has recently emerged as a promising therapeutic strategy for the treatment and chemosensitization of tumors, and has already demonstrated positive clinical results in patients. In this review, the dual role of autophagy during carcinogenesis is discussed and current therapeutic strategies aimed at targeting autophagy for the treatment of cancer, both under preclinical and clinical development, are presented. The use of autophagy modulators in combination therapies, in order to overcome drug resistance during cancer treatment, is also discussed as well as the potential challenges and limitations for the use of these novel therapeutic strategies in the clinic.

scholarly journals Endoplasmic Reticulum–Mitochondria Contacts Are Required for Pexophagy in Saccharomyces cerevisiae

Contact ◽  
2019 ◽  
Vol 2 ◽  
pp. 251525641882158 ◽  
Author(s):  
Xu Liu ◽  
Xin Wen ◽  
Daniel J. Klionsky
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Endoplasmic Reticulum ◽  
Lipid Metabolism ◽  
Membrane Protein ◽  
Mutant Form ◽  
Peroxisomal Membrane ◽  
Cellular Homeostasis ◽  
Selective Autophagy ◽  
Contact Sites ◽  
Autophagic Degradation

Peroxisomes play important roles in lipid metabolism. Surplus or damaged peroxisomes can be selectively targeted for autophagic degradation, a process termed pexophagy. Maintaining a proper level of pexophagy is critical for cellular homeostasis. Here, we found that endoplasmic reticulum (ER)–mitochondria contact sites are necessary for efficient pexophagy. During pexophagy, the peroxisomes destined for degradation are adjacent to the ER–mitochondria encounter structure (ERMES) that mediates the formation of ER–mitochondria contacts; disruption of the ERMES results in a severe defect in pexophagy. We show that a mutant form of Mdm34, a component of the ERMES, which impairs ERMES formation and diminishes its association with the peroxisomal membrane protein Pex11, also causes defects in pexophagy. The dynamin-related GTPase Vps1, which is specific for peroxisomal fission, is recruited to the peroxisomes at ER–mitochondria contacts by the selective autophagy scaffold Atg11 and the pexophagy receptor Atg36, facilitating peroxisome degradation.

scholarly journals The Role of Autophagy in Inflammatory Bowel Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Bo-Zong Shao ◽  
Yi Yao ◽  
Jun-Shan Zhai ◽  
Jian-Hua Zhu ◽  
Jin-Ping Li ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Responses ◽  
Bowel Disease ◽  
Recent Literature ◽  
Therapeutic Strategies ◽  
Inflammatory Bowel ◽  
Intestinal Inflammatory Disease ◽  
Novel Therapeutic Strategies ◽  
Catabolic Process

Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory disease, including ulcerative colitis (UC) and Crohn’s disease (CD). The abnormality of inflammatory and immune responses in the intestine contributes to the pathogenesis and progression of IBD. Autophagy is a vital catabolic process in cells. Recent studies report that autophagy is highly involved in various kinds of diseases, especially inflammation-related diseases, such as IBD. In this review, the biological characteristics of autophagy and its role in IBD will be described and discussed based on recent literature. In addition, several therapies for IBD through modulating the inflammasome and intestinal microbiota taking advantage of autophagy regulation will be introduced. We aim to bring new insight in the exploration of mechanisms for IBD and development of novel therapeutic strategies against IBD.

scholarly journals Atlastins remodel the endoplasmic reticulum for selective autophagy

2018 ◽  
Vol 217 (10) ◽  
pp. 3354-3367 ◽  
Author(s):  
Jin Rui Liang ◽  
Emily Lingeman ◽  
Saba Ahmed ◽  
Jacob E. Corn
Keyword(s):  
Endoplasmic Reticulum ◽  
Family Members ◽  
Gtpase Domain ◽  
Selective Autophagy ◽  
Membrane Morphology ◽  
Reporter Systems ◽  
Autophagic Degradation ◽  
Specific Receptors ◽  
Starvation Conditions ◽  
Er Membrane

Specific receptors are required for the autophagic degradation of endoplasmic reticulum (ER), known as ER-phagy. However, little is known about how the ER is remodeled and separated for packaging into autophagosomes. We developed two ER-phagy–specific reporter systems and found that Atlastins are key positive effectors and also targets of ER-phagy. Atlastins are ER-resident GTPases involved in ER membrane morphology, and Atlastin-depleted cells have decreased ER-phagy under starvation conditions. Atlastin’s role in ER-phagy requires a functional GTPase domain and proper ER localization, both of which are also involved in ER architecture. The three Atlastin family members functionally compensate for one another during ER-phagy and may form heteromeric complexes with one another. We further find that Atlastins act downstream of the FAM134B ER-phagy receptor, such that depletion of Atlastins represses ER-autophagy induced by the overexpression of FAM134B. We propose that during ER-phagy, Atlastins remodel ER membrane to separate pieces of FAM134B-marked ER for efficient autophagosomal engulfment.

Sign in / Sign up

Export Citation Format

Share Document