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JOURNAL ARTICLE
Yuki Hayashi, Hidenori Ichijo
Proteostasis of the endoplasmic reticulum (ER) is maintained by coordinated action of two major catabolic pathways: proteasome-dependent ER-associated degradation (ERAD) and less characterized lysosomal pathways. Recent studies on ER-specific autophagy (termed "reticulophagy") have highlighted the importance of lysosomes for ER proteostasis. Key to this process are proteins termed reticulophagy receptors that connect ER fragments and Atg8-family proteins, facilitating the lysosomal degradation of both native and aberrant ER proteins in a relatively nonselective manner...
April 10, 2024: Autophagy
#2
JOURNAL ARTICLE
Jiajia Wang, Pengyu Fan, Peng Shen, Cong Fan, Pan Zhao, Yao Shen, Kewei Dong, Rui Ling, Suning Chen, Jian Zhang
Cancer cells employ the unfolded protein response (UPR) or induce autophagy, especially selective removal of certain ER domains via reticulophagy (termed ER-phagy), to mitigate endoplasmic reticulum (ER) stress for ER homeostasis when encountering microenvironmental stress. N6-methyladenosine (m6A) is one of the most abundant epitranscriptional modifications and plays important roles in various biological processes. However, the molecular mechanism of m6A modification in the ER stress response is poorly understood...
April 4, 2024: Cancer Letters
#3
JOURNAL ARTICLE
Alexandra Stolz
Tuning and assimilation of endoplasmic reticulum (ER) content in each cell of the human body is an essential part of organismal homeostasis and adaptation to stress. As such, the lysosomal turnover of ER (reticulophagy) needs to be regulated in a spatio-temporal as well as cell-type specific manner. We recently identified CSNK2/CK2 (casein kinase 2) as the enzyme that phosphorylates the reticulophagy receptors RETREG1/FAM134B and RETREG3/FAM134C and regulates their activity. Phosphorylation of the receptors is a prerequisite for their subsequent functional ubiquitination and the formation of high-density clusters, presumably representing active macroautophagy/autophagy sites at the ER membrane...
March 21, 2024: Autophagy
#4
EDITORIAL
Zhangyuan Yin, Daniel J Klionsky
The selective clearance of unwanted, damaged or dangerous components by macroautophagy/autophagy is critical for maintaining cellular homeostasis in organisms from yeast to humans. In recent years, significant progress has been made in understanding how phagophores selectively sequester specific cargo. Nevertheless, a fundamental question remains: Can distinct selective autophagy programs simultaneously operate within the same cell? A recent study from the Baehrecke lab has unveiled a developmentally programmed Pink1-dependent reticulophagy process in the Drosophila intestine...
March 8, 2024: Autophagy
#5
REVIEW
Xin Chen, Andrey S Tsvetkov, Han-Ming Shen, Ciro Isidoro, Nicholas T Ktistakis, Andreas Linkermann, Werner J H Koopman, Hans-Uwe Simon, Lorenzo Galluzzi, Shouqing Luo, Daqian Xu, Wei Gu, Olivier Peulen, Qian Cai, David C Rubinsztein, Jen-Tsan Chi, Donna D Zhang, Changfeng Li, Shinya Toyokuni, Jinbao Liu, Jong-Lyel Roh, Enyong Dai, Gabor Juhasz, Wei Liu, Jianhua Zhang, Minghua Yang, Jiao Liu, Ling-Qiang Zhu, Weiping Zou, Mauro Piacentini, Wen-Xing Ding, Zhenyu Yue, Yangchun Xie, Morten Petersen, David A Gewirtz, Michael A Mandell, Charleen T Chu, Debasish Sinha, Eftekhar Eftekharpour, Boris Zhivotovsky, Sébastien Besteiro, Dmitry I Gabrilovich, Do-Hyung Kim, Valerian E Kagan, Hülya Bayir, Guang-Chao Chen, Scott Ayton, Jan D Lünemann, Masaaki Komatsu, Stefan Krautwald, Ben Loos, Eric H Baehrecke, Jiayi Wang, Jon D Lane, Junichi Sadoshima, Wan Seok Yang, Minghui Gao, Christian Münz, Michael Thumm, Martin Kampmann, Di Yu, Marta M Lipinski, Jace W Jones, Xuejun Jiang, Herbert J Zeh, Rui Kang, Daniel J Klionsky, Guido Kroemer, Daolin Tang
Macroautophagy/autophagy is a complex degradation process with a dual role in cell death that is influenced by the cell types that are involved and the stressors they are exposed to. Ferroptosis is an iron-dependent oxidative form of cell death characterized by unrestricted lipid peroxidation in the context of heterogeneous and plastic mechanisms. Recent studies have shed light on the involvement of specific types of autophagy (e.g. ferritinophagy, lipophagy, and clockophagy) in initiating or executing ferroptotic cell death through the selective degradation of anti-injury proteins or organelles...
March 5, 2024: Autophagy
#6
JOURNAL ARTICLE
Yiwei Sun, Xi Wang
The lysosomal degradation of the endoplasmic reticulum (ER), known as "reticulophagy", is important for protein quality control and organelle turnover. Here we present a noncanonical reticulophagy occurring at ER exit sites (ERESs) induced by the misfolded SERPINA1/α1-antitrypsin (AAT) mutant, Z-AAT. The accumulation of Z-AAT arrests ER-to-Golgi transport, and recruits V-ATPase and ATG16L1 to mediate LC3C decoration of ERESs. Consequently, the receptor RETREG1/FAM134B-2 is recruited by lipidated LC3C to initiate reticulophagy...
February 13, 2024: Autophagy
#7
REVIEW
Suwei Jin, Yujia Li, Tianji Xia, Yongguang Liu, Shanshan Zhang, Hongbo Hu, Qi Chang, Mingzhu Yan
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide, whereas there is no approved drug therapy for it due to its complexity. Studies are emerging to discuss the role of selective autophagy in the pathogenesis of NAFLD, because the specificity among the features of selective autophagy makes it a crucial process in mitigating hepatocyte damage caused by aberrant accumulation of dysfunctional organelles, for which no other pathway can compensate...
January 29, 2024: Journal of Advanced Research
#8
JOURNAL ARTICLE
Ning Xu, Yingbo Liang, Jun Liu
Selective degradation of the endoplasmic reticulum (ER) by macroautophagy/autophagy (reticulophagy) is essential for maintaining ER morphology and homeostasis under environmental stresses. Several reticulophagy receptors have been identified in mammals and yeast, but their counterparts in plants have not been extensively explored yet. Recently, we demonstrated that the HVA22-family protein OsHLP1 is a reticulophagy receptor in rice plants, and its orthologs function similarly in Arabidopsis plants. In this punctum, we discuss why the HVA22 family proteins are the reticulophagy receptors in plants and how reticulophagy is highly associated with plant immune response...
January 31, 2024: Autophagy
#9
JOURNAL ARTICLE
Chen-Xi Zou, Li-Lin Du
Under stress conditions, the endoplasmic reticulum and nucleus undergo turnover through selective macroautophagy/autophagy processes termed reticulophagy and nucleophagy, respectively. Our recent study has identified the protein Hva22/Rop1/Yep1, a member of the REEP1-REEP4 subfamily of the REEP protein family, as an essential factor for both processes in the fission yeast Schizosaccharomyces pombe . In the absence of Hva22/Yep1, reticulophagy and nucleophagy cargos without surrounding autophagic membranes accumulate in the cytoplasm...
January 1, 2024: Autophagy
#10
JOURNAL ARTICLE
Marika K Kucińska, Maurizio Molinari
The endoplasmic reticulum (ER) extends to the outer (ONM) and the inner (INM) nuclear membrane forming the nuclear envelope (NE) that delimits the nucleoplasm containing the cell genome. Unfolded protein responses (UPRs) and reticulophagy responses increase or reduce ER size and activities, respectively. If dynamic changes of the ER are transmitted to the contiguous NE was not known. In our recent publication, we report on the transmission of stress-induced ER expansion to the NE, which requires disassembly of the Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes deputed to ensure a physical connection between the cytoplasmic cytoskeleton and the nuclear lamina and to maintain the width between INM and ONM within 50 nm...
December 28, 2023: Autophagy
#11
JOURNAL ARTICLE
Jiantao Zhang, Ruth Cruz-Cosme, Chenyu Zhang, Dongxiao Liu, Qiyi Tang, Richard Y Zhao
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has tragically claimed millions of lives through coronavirus disease 2019 (COVID-19), and there remains a critical gap in our understanding of the precise molecular mechanisms responsible for the associated fatality. One key viral factor of interest is the SARS-CoV-2 ORF3a protein, which has been identified as a potent inducer of host cellular proinflammatory responses capable of triggering the catastrophic cytokine storm, a primary contributor to COVID-19-related deaths...
January 16, 2024: MBio
#12
JOURNAL ARTICLE
Xuehong Qian, Jiajia Sun, Yixian Cui
Reticulophagy is a selective autophagy of the endoplasmic reticulum (ER) mediated by cargo receptors. It plays a crucial role in ER quality control, yet the mechanisms that initiate reticulophagy remain poorly understood. Our study identified the multifunctional protein UVRAG (UV radiation resistance associated gene) as a novel regulator of reticulophagy. UVRAG interacts with sheet and tubular reticulophagy receptors, regulates the oligomerization of receptors and facilitates their interaction with LC3/GABARAP, critical for ER fragmentation and autophagosome targeting...
December 6, 2023: Autophagy
#13
JOURNAL ARTICLE
Ling Bai, Rui Zhang, Haixue Zheng, Zhixiong Zhang, Zhidong Zhang, Yanmin Li
Seneca Valley Virus (SVV), a member of the Picornaviridae family, is an emerging porcine virus that can cause vesicular disease in pigs. However, the immune evasion mechanism of SVV remains unclear, as does its interaction with other pathways. STING (Stimulator of interferon genes) is typically recognized as a critical factor in innate immune responses to DNA virus infection, but its role during SVV infection remains poorly understood. In the present study, we observed that STING was degraded in SVV-infected PK-15 cells, and SVV replication in the cells was affected when STING was knockdown or overexpressed...
November 3, 2023: Viruses
#14
JOURNAL ARTICLE
Patrick Lüningschrör, Michael Sendtner
Tightly regulated cell surface expression of NTRK2/TrkB provides a mechanism for fine-tuning cellular responses to the neurotrophic factor BDNF. Recently, the degradation of NTRK2 by reticulophagy has been identified as a mechanism to limit its availability for trafficking to the cell membrane. The ER-chaperone CANX (calnexin) delivers NTRK2 to the reticulophagy receptor RETREG1/Fam134b for lysosomal degradation. Upon phosphorylation of CANX, NTRK2 is released from this complex, which facilitates its cell surface transport...
November 8, 2023: Autophagy
#15
JOURNAL ARTICLE
Y Duan, R Q Yao, L Y Zheng, N Dong, Y Wu, Y M Yao, X G Dai
Objective: To investigate the influence of family with sequence similarity 134, member B (FAM134B)-mediated reticulophagy on lipopolysaccharide (LPS)-induced apoptosis of mouse dendritic cells (DCs), so as to provide a basis for improving the immune suppression of sepsis caused by wound infection and other factors. Methods: The experimental research methods were used. The DC line DC2.4 of the 3rd to 10th passage in the logarithmic growth stage was collected for experiments. DCs were divided into LPS stimulation 0 h (no stimulation) group, LPS stimulation 6 h group, LPS stimulation 12 h group, LPS stimulation 24 h group, and LPS stimulation 72 h group, which were cultured with 1 μg/mL LPS (the same concentration below) for the corresponding time...
September 20, 2023: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
#16
JOURNAL ARTICLE
Jia-Yao Li, Tian Tian, Bing Han, Ting Yang, Yi-Xin Guo, Jia-Yu Wu, Yu-Si Chen, Qin Yang, Ru-Jia Xie
BACKGROUND: Hepatocellular carcinoma (HCC) is a common clinical condition with a poor prognosis and few effective treatment options. Potent anticancer agents for treating HCC must be identified. Epigenetics plays an essential role in HCC tumorigenesis. Suberoylanilide hydroxamic acid (SAHA), the most common histone deacetylase inhibitor agent, triggers many forms of cell death in HCC. However, the underlying mechanism of action remains unclear. Family with sequence similarity 134 member B (FAM134B)-induced reticulophagy, a selective autophagic pathway, participates in the decision of cell fate and exhibits anticancer activity...
September 14, 2023: World Journal of Gastroenterology: WJG
#17
JOURNAL ARTICLE
Julien A Clain, Steven Boutrais, Juliette Dewatines, Gina Racine, Henintsoa Rabezanahary, Arnaud Droit, Ouafa Zghidi-Abouzid, Jérôme Estaquier
While liver inflammation is associated with AIDS, little is known so far about hepatic CD4+ T cells. By using the simian immunodeficiency virus (SIV)-infected rhesus macaque (RM) model, we aimed to characterize CD4+ T cells. The phenotype of CD4+ T cells was assessed by flow cytometry from uninfected ( n = 3) and infected RMs, with either SIVmac251 ( n = 6) or SHIVSF162p3 ( n = 6). After cell sorting of hepatic CD4+ T cells, viral DNA quantification and RNA sequencing were performed.Thus, we demonstrated that liver CD4+ T cells strongly expressed the SIV coreceptor, CCR5...
September 1, 2023: Microbiology Spectrum
#18
JOURNAL ARTICLE
Xinyi Wang, Boran Li, Qiming Sun
Reticulophagy is an evolutionarily conserved mechanism essential to maintain the endoplasmic reticulum (ER) homeostasis. A series of studies identified a panel of reticulophagy receptors. However, it remains unclear how these receptors sense upstream signals for spatiotemporal control of reticulophagy and how ER is fragmented into small pieces for sequestration into phagophores. Recently, we and others showed that the oligomerization of RETREG1/FAM134B (reticulophagy regulator 1), an reticulophagy receptor, triggers the scission of ER membrane to facilitate reticulophagy...
August 31, 2023: Autophagy
#19
JOURNAL ARTICLE
Tao Bi, Qianqian Lu, Xiaohong Pan, Fenglin Dong, Yejia Hu, Zongzhen Xu, Peng Xiu, Zhiqian Liu, Jie Li
Ferroptosis is an important mode of regulated cell death (RCD). Its inhibition is closely related to therapeutic resistance and poor prognosis in hepatocellular carcinoma (HCC). Previous reports have demonstrated ferroptosis as a biological process highly dependent on selective autophagy, such as ferritinophagy, lipophagy, and clockophagy. Our study also revealed a role for ER-phagy-mediated ferroptosis in HCC cells treated with multi-targeted tyrosine kinase inhibitors (TKIs). In the current study, we found that the homologous circular RNA (circRNA) of the family with sequence similarity 134, member B ( FAM134B ), hsa_circ_0128505 (was abbreviated as circFAM134B in the present study), was identified to specifically target ER-phagy to promote lenvatinib (LV)-induced ferroptosis using reactive oxygen species (ROS), Fe2+ , malondialdehyde (MDA), and western blot (WB) assays in HCC cells...
August 21, 2023: Cell Cycle
#20
REVIEW
Mohd Shariq, Asrar A Malik, Javaid A Sheikh, Seyed E Hasnain, Nasreen Z Ehtesham
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) regulates autophagic flux by blocking the fusion of autophagosomes with lysosomes, causing the accumulation of membranous vesicles for replication. Multiple SARS-CoV-2 proteins regulate autophagy with significant roles attributed to ORF3a. Mechanistically, open reading frame 3a (ORF3a) forms a complex with UV radiation resistance associated, regulating the functions of the PIK3C3-1 and PIK3C3-2 lipid kinase complexes, thereby modulating autophagosome biogenesis...
July 2023: Journal of Medical Virology
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