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Autophagy in protists and their hosts: When, how and why? 原生生物及其宿主的自噬:何时、如何以及为何?
Autophagy reports Pub Date : 2023-01-01 Epub Date: 2023-03-09 DOI: 10.1080/27694127.2022.2149211
Patricia Silvia Romano, Takahiko Akematsu, Sébastien Besteiro, Annina Bindschedler, Vern B Carruthers, Zeinab Chahine, Isabelle Coppens, Albert Descoteaux, Thabata Lopes Alberto Duque, Cynthia Y He, Volker Heussler, Karine G Le Roch, Feng-Jun Li, Juliana Perrone Bezerra de Menezes, Rubem Figueiredo Sadok Menna-Barreto, Jeremy C Mottram, Jacqueline Schmuckli-Maurer, Boris Turk, Patricia Sampaio Tavares Veras, Betiana Nebai Salassa, María Cristina Vanrell
{"title":"Autophagy in protists and their hosts: When, how and why?","authors":"Patricia Silvia Romano, Takahiko Akematsu, Sébastien Besteiro, Annina Bindschedler, Vern B Carruthers, Zeinab Chahine, Isabelle Coppens, Albert Descoteaux, Thabata Lopes Alberto Duque, Cynthia Y He, Volker Heussler, Karine G Le Roch, Feng-Jun Li, Juliana Perrone Bezerra de Menezes, Rubem Figueiredo Sadok Menna-Barreto, Jeremy C Mottram, Jacqueline Schmuckli-Maurer, Boris Turk, Patricia Sampaio Tavares Veras, Betiana Nebai Salassa, María Cristina Vanrell","doi":"10.1080/27694127.2022.2149211","DOIUrl":"10.1080/27694127.2022.2149211","url":null,"abstract":"<p><p>Pathogenic protists are a group of organisms responsible for causing a variety of human diseases including malaria, sleeping sickness, Chagas disease, leishmaniasis, and toxoplasmosis, among others. These diseases, which affect more than one billion people globally, mainly the poorest populations, are characterized by severe chronic stages and the lack of effective antiparasitic treatment. Parasitic protists display complex life-cycles and go through different cellular transformations in order to adapt to the different hosts they live in. Autophagy, a highly conserved cellular degradation process, has emerged as a key mechanism required for these differentiation processes, as well as other functions that are crucial to parasite fitness. In contrast to yeasts and mammals, protist autophagy is characterized by a modest number of conserved autophagy-related proteins (ATGs) that, even though, can drive the autophagosome formation and degradation. In addition, during their intracellular cycle, the interaction of these pathogens with the host autophagy system plays a crucial role resulting in a beneficial or harmful effect that is important for the outcome of the infection. In this review, we summarize the current state of knowledge on autophagy and other related mechanisms in pathogenic protists and their hosts. We sought to emphasize when, how, and why this process takes place, and the effects it may have on the parasitic cycle. A better understanding of the significance of autophagy for the protist life-cycle will potentially be helpful to design novel anti-parasitic strategies.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9324014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Kinetics of autophagic activity in nanoparticle-exposed lung adenocarcinoma (A549) cells. 暴露于纳米粒子的肺腺癌(A549)细胞自噬活性动力学。
Autophagy reports Pub Date : 2023-01-01 Epub Date: 2023-03-15 DOI: 10.1080/27694127.2023.2186568
Arnold Sipos, Kwang-Jin Kim, Constantinos Sioutas, Edward D Crandall
{"title":"Kinetics of autophagic activity in nanoparticle-exposed lung adenocarcinoma (A549) cells.","authors":"Arnold Sipos, Kwang-Jin Kim, Constantinos Sioutas, Edward D Crandall","doi":"10.1080/27694127.2023.2186568","DOIUrl":"10.1080/27694127.2023.2186568","url":null,"abstract":"<p><p>Autophagy, a homeostatic mechanism, is crucial in maintaining normal cellular function. Although dysregulation of autophagic processes is recognized in certain diseases, it is unknown how maintenance of cellular homeostasis might be affected by the kinetics of autophagic activity in response to various stimuli. In this study, we assessed those kinetics in lung adenocarcinoma (A549) cells in response to exposure to nanoparticles (NP) and/or Rapamycin. Since NP are known to induce autophagy, we wished to determine if this phenomenon could be a driver of the harmful effects seen in lung tissues exposed to air pollution. A549 cells were loaded with a fluorescent marker (DAPRed) that labels autophagosomes and autolysosomes. Autophagic activity was assessed based on the fluorescence intensity of DAPRed measured over the entire cell volume of live single cells using confocal laser scanning microscopy (CLSM). Autophagic activity over time was determined during exposure of A549 cells to single agents (50 nM Rapamycin; 80 μg/mL, 20 nm carboxylated polystyrene NP (PNP); or, 1 μg/mL ambient ultrafine particles (UFP) (<180 nm)), or double agents (Rapamycin + PNP or Rapamycin + UFP; concomitant and sequential), known to stimulate autophagy. Autophagic activity increased in all experimental modalities, including both single agent and double agent exposures, and reached a steady state in all cases ~2 times control from ~8 to 24 hrs, suggesting the presence of an upper limit to autophagic capacity. These results are consistent with the hypothesis that environmental stressors might exert their harmful effects, at least in part, by limiting available autophagic response to additional stimulation, thereby making nanoparticle-exposed cells more susceptible to secondary injury due to autophagic overload.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10373127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9945538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Topoisomerase I poisons-induced autophagy: Cytoprotective, Cytotoxic or Non-protective. 拓扑异构酶 I 毒物诱导的自噬:细胞保护作用、细胞毒性或无保护作用
Autophagy reports Pub Date : 2023-01-01 Epub Date: 2022-12-25 DOI: 10.1080/27694127.2022.2155904
Ahmed M Elshazly, Polina A Wright, Jingwen Xu, David A Gewirtz
{"title":"Topoisomerase I poisons-induced autophagy: Cytoprotective, Cytotoxic or Non-protective.","authors":"Ahmed M Elshazly, Polina A Wright, Jingwen Xu, David A Gewirtz","doi":"10.1080/27694127.2022.2155904","DOIUrl":"10.1080/27694127.2022.2155904","url":null,"abstract":"<p><p>Topoisomerase I inhibitors represent a widely used class of antineoplastic agents that promote both single-stranded and double-stranded breaks in the DNA of tumor cells, leading to tumor cell death. Topotecan and irinotecan are the clinically relevant derivatives of the parent drug, camptothecin. As is the case with many if not most anticancer agents, irinotecan and topotecan promote autophagy. However, whether the autophagy is cytotoxic, cytoprotective, or non-protective is not clearly defined, and may depend largely upon the genetic background of the tumor cell being investigated. This review explores the available literature regarding the nature of the autophagy induced by these clinically utilized topoisomerase I inhibitors in preclinical tumor models with the goal of determining whether the targeting of autophagy might have potential as a therapeutic strategy to enhance the antitumor response and/or overcome drug resistance.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"2 1","pages":"1-16"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9153810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Shear stress induces autophagy in Schlemm's canal cells via primary cilia-mediated SMAD2/3 signaling pathway. 剪切应力通过初级纤毛介导的 SMAD2/3 信号通路诱导 Schlemm 管细胞自噬。
Autophagy reports Pub Date : 2023-01-01 Epub Date: 2023-07-20 DOI: 10.1080/27694127.2023.2236519
Myoung Sup Shim, Angela Dixon, April Nettesheim, Kristin M Perkumas, W Daniel Stamer, Yang Sun, Paloma B Liton
{"title":"Shear stress induces autophagy in Schlemm's canal cells via primary cilia-mediated SMAD2/3 signaling pathway.","authors":"Myoung Sup Shim, Angela Dixon, April Nettesheim, Kristin M Perkumas, W Daniel Stamer, Yang Sun, Paloma B Liton","doi":"10.1080/27694127.2023.2236519","DOIUrl":"10.1080/27694127.2023.2236519","url":null,"abstract":"<p><p>The Schlemm's canal (SC) is a circular, lymphatic-like vessel located at the limbus of the eye that participates in the regulation of aqueous humor drainage to control intraocular pressure (IOP). Circumferential flow of aqueous humor within the SC lumen generates shear stress, which regulates SC cell behaviour. Using biochemical analysis and real-time live cell imaging techniques, we have investigated the activation of autophagy in SC cells by shear stress. We report, for the first time, the primary cilium (PC)-dependent activation of autophagy in SC cells in response to shear stress. Moreover, we identified PC-dependent shear stress-induced autophagy to be positively regulated by phosphorylation of SMAD2 in its linker and C-terminal regions. Additionally, SMAD2/3 signaling was found to transcriptionally activate <i>LC3B</i>, <i>ATG5</i> and <i>ATG7</i> in SC cells. Intriguingly, concomitant to SMAD2-dependent activation of autophagy, we also report here the activation of mTOR pathway, a classical autophagy inhibitor, in SC cells by shear stress. mTOR activation was found to also be dependent on the PC. Moreover, pharmacological inhibition of class I PI3K increased phosphorylation of SMAD2 at the linker and activated autophagy. Together, our data indicates an interplay between PI3K and SMAD2/3 signaling pathways in the regulation of PC-dependent shear stress-induced autophagy in SC cells.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10492986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chaperone-Mediated Autophagy Regulates Hypoxic Pathology in Cardiomyocytes. Chaperone介导的自噬调节心肌细胞缺氧病理
Autophagy reports Pub Date : 2023-01-01 Epub Date: 2023-02-07 DOI: 10.1080/27694127.2023.2174337
Rajeshwary Ghosh, J Scott Pattison
{"title":"Chaperone-Mediated Autophagy Regulates Hypoxic Pathology in Cardiomyocytes.","authors":"Rajeshwary Ghosh, J Scott Pattison","doi":"10.1080/27694127.2023.2174337","DOIUrl":"10.1080/27694127.2023.2174337","url":null,"abstract":"<p><p>Tight regulation of protein degradation pathways is essential for maintaining cardiac homeostasis. The goal of this work was to define the role of chaperone-mediated autophagy (CMA), in cardiomyocytes. CMA acts as a selective degradation pathway of proteins using a cytosolic and lysosomal co-chaperone, HSPA8/HSC70, and the CMA-specific LAMP2A (lysosomal-associated membrane protein 2A) receptor. LAMP2A protein levels are known to be necessary for CMA function. While CMA was shown to exert protection against neurodegenerative disorders and cancer, the role of CMA during cardiac pathology was not known. It was hypothesized that enhancing CMA could mitigate hypoxic pathology in cardiomyocytes. Thus, a genetic gain- and loss-of-CMA-function approach was employed using a <i>Lamp2a</i>-overexpressing adenovirus and a <i>Lamp2a</i>-silencing siRNA, respectively, in primary cardiomyocytes treated with CoCl<sub>2</sub> (a hypoxia-mimetic agent) or vehicle control. The experiments performed clearly showed that <i>Lamp2a</i>-overexpression leads to CMA activation that is sufficient to attenuate hypoxia-induced cardiomyocyte death and toxicity.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45102936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Parkin-dependent mitophagy occurs via proteasome-dependent steps sequentially targeting separate mitochondrial sub-compartments for autophagy 帕金森依赖性线粒体自噬通过蛋白酶体依赖性步骤依次靶向单独的线粒体亚室进行自噬
Autophagy reports Pub Date : 2022-12-19 DOI: 10.1080/27694127.2022.2143214
Anna Lechado-Terradas, Sandra Schepers, Katharina I. Zittlau, Karan Sharma, Orkun Ok, J. Fitzgerald, S. Geimer, B. Westermann, B. Maček, P. Kahle
{"title":"Parkin-dependent mitophagy occurs via proteasome-dependent steps sequentially targeting separate mitochondrial sub-compartments for autophagy","authors":"Anna Lechado-Terradas, Sandra Schepers, Katharina I. Zittlau, Karan Sharma, Orkun Ok, J. Fitzgerald, S. Geimer, B. Westermann, B. Maček, P. Kahle","doi":"10.1080/27694127.2022.2143214","DOIUrl":"https://doi.org/10.1080/27694127.2022.2143214","url":null,"abstract":"","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41732847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ULK1 in autophagy: sugar it up 自噬中的ULK1,加糖
Autophagy reports Pub Date : 2022-10-31 DOI: 10.1080/27694127.2022.2139878
Sheng Yan, Jing Li
{"title":"ULK1 in autophagy: sugar it up","authors":"Sheng Yan, Jing Li","doi":"10.1080/27694127.2022.2139878","DOIUrl":"https://doi.org/10.1080/27694127.2022.2139878","url":null,"abstract":"","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48637407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Let them eat virus: exploring how TBK1 (TANK binding kinase 1) enhances autophagic flux to promote autophagic degradation of coxsackievirus B 让它们吃掉病毒:探索TBK1(TANK结合激酶1)如何增强自噬流量以促进柯萨奇病毒B的自噬降解
Autophagy reports Pub Date : 2022-10-31 DOI: 10.1080/27694127.2022.2139332
S. Sawaged, Jon Sin
{"title":"Let them eat virus: exploring how TBK1 (TANK binding kinase 1) enhances autophagic flux to promote autophagic degradation of coxsackievirus B","authors":"S. Sawaged, Jon Sin","doi":"10.1080/27694127.2022.2139332","DOIUrl":"https://doi.org/10.1080/27694127.2022.2139332","url":null,"abstract":"","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45498390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The ART of Resistance 抵抗的艺术
Autophagy reports Pub Date : 2022-10-26 DOI: 10.1080/27694127.2022.2134254
Ananya Ray, N. Surolia
{"title":"The ART of Resistance","authors":"Ananya Ray, N. Surolia","doi":"10.1080/27694127.2022.2134254","DOIUrl":"https://doi.org/10.1080/27694127.2022.2134254","url":null,"abstract":"","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46507003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The missing link: TBK1 connects membrane damage sensing with autophagic response upon adenovirus entry 缺失的一环:TBK1连接腺病毒进入时膜损伤感知与自噬反应
Autophagy reports Pub Date : 2022-10-25 DOI: 10.1080/27694127.2022.2136604
Coralie F. Daussy, Noémie Pied, F. Rayne, H. Wodrich
{"title":"The missing link: TBK1 connects membrane damage sensing with autophagic response upon adenovirus entry","authors":"Coralie F. Daussy, Noémie Pied, F. Rayne, H. Wodrich","doi":"10.1080/27694127.2022.2136604","DOIUrl":"https://doi.org/10.1080/27694127.2022.2136604","url":null,"abstract":"","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41466758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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