Pub Date : 2024-01-01Epub Date: 2024-12-07DOI: 10.1080/27694127.2024.2434379
Zahra Baninameh, Jens O Watzlawik, Xu Hou, Tyrique Richardson, Nicholas W Kurchaba, Tingxiang Yan, Damian N Di Florio, DeLisa Fairweather, Lu Kang, Justin H Nguyen, Takahisa Kanekiyo, Dennis W Dickson, Sachiko Noda, Shigeto Sato, Nobutaka Hattori, Matthew S Goldberg, Ian G Ganley, Kelly L Stauch, Fabienne C Fiesel, Wolfdieter Springer
The ubiquitin kinase-ligase pair PINK1-PRKN identifies and selectively marks damaged mitochondria for elimination via the autophagy-lysosome system (mitophagy). While this cytoprotective pathway has been extensively studied in vitro upon acute and complete depolarization of mitochondria, the significance of PINK1-PRKN mitophagy in vivo is less well established. Here we used a novel approach to study PINK1-PRKN signaling in different energetically demanding tissues of mice during normal aging. We demonstrate a generally increased expression of both genes and enhanced enzymatic activity with aging across tissue types. Collectively our data suggest a distinct regulation of PINK1-PRKN signaling under basal conditions with the most pronounced activation and flux of the pathway in mouse heart compared to brain or skeletal muscle. Our biochemical analyses complement existing mitophagy reporter readouts and provide an important baseline assessment in vivo, setting the stage for further investigations of the PINK1-PRKN pathway during stress and in relevant disease conditions.
{"title":"Alterations of PINK1-PRKN signaling in mice during normal aging.","authors":"Zahra Baninameh, Jens O Watzlawik, Xu Hou, Tyrique Richardson, Nicholas W Kurchaba, Tingxiang Yan, Damian N Di Florio, DeLisa Fairweather, Lu Kang, Justin H Nguyen, Takahisa Kanekiyo, Dennis W Dickson, Sachiko Noda, Shigeto Sato, Nobutaka Hattori, Matthew S Goldberg, Ian G Ganley, Kelly L Stauch, Fabienne C Fiesel, Wolfdieter Springer","doi":"10.1080/27694127.2024.2434379","DOIUrl":"10.1080/27694127.2024.2434379","url":null,"abstract":"<p><p>The ubiquitin kinase-ligase pair PINK1-PRKN identifies and selectively marks damaged mitochondria for elimination via the autophagy-lysosome system (mitophagy). While this cytoprotective pathway has been extensively studied <i>in vitro</i> upon acute and complete depolarization of mitochondria, the significance of PINK1-PRKN mitophagy <i>in vivo</i> is less well established. Here we used a novel approach to study PINK1-PRKN signaling in different energetically demanding tissues of mice during normal aging. We demonstrate a generally increased expression of both genes and enhanced enzymatic activity with aging across tissue types. Collectively our data suggest a distinct regulation of PINK1-PRKN signaling under basal conditions with the most pronounced activation and flux of the pathway in mouse heart compared to brain or skeletal muscle. Our biochemical analyses complement existing mitophagy reporter readouts and provide an important baseline assessment <i>in vivo</i>, setting the stage for further investigations of the PINK1-PRKN pathway during stress and in relevant disease conditions.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11855339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506516","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}
Pub Date : 2024-01-01Epub Date: 2024-10-23DOI: 10.1080/27694127.2024.2418256
Pariyamon Thaprawat, Zhihai Zhang, Eric C Rentchler, Fengrong Wang, Shreya Chalasani, Christopher J Giuliano, Sebastian Lourido, Manlio Di Cristina, Daniel J Klionsky, Vern B Carruthers
Toxoplasma gondii is a ubiquitous protozoan parasite that can reside long-term within hosts as intracellular tissue cysts comprised of chronic stage bradyzoites. To perturb chronic infection requires a better understanding of the cellular processes that mediate parasite persistence. Macroautophagy/autophagy is a catabolic and homeostatic pathway that is required for T. gondii chronic infection, although the molecular details of this process remain poorly understood. A key step in autophagy is the initial formation of the phagophore that sequesters cytoplasmic components and matures into a double-membraned autophagosome for delivery of the cargo to a cell's digestive organelle for degradative recycling. While T. gondii appears to have a reduced repertoire of autophagy proteins, it possesses a putative phospholipid scramblase, TgATG9. Through structural modeling and complementation assays, we show herein that TgATG9 can partially rescue bulk autophagy in atg9Δ yeast. We demonstrated the importance of TgATG9 for proper autophagosome dynamics at the subcellular level using three-dimensional live cell lattice light sheet microscopy. Conditional knockdown of TgATG9 in T. gondii after bradyzoite differentiation resulted in markedly reduced parasite viability. Together, our findings provide insights into the molecular dynamics of autophagosome biogenesis within an early-branching eukaryote and pinpoint the indispensable role of autophagy in maintaining T. gondii chronic infection.
{"title":"TgATG9 is required for autophagosome biogenesis and maintenance of chronic infection in <i>Toxoplasma gondii</i>.","authors":"Pariyamon Thaprawat, Zhihai Zhang, Eric C Rentchler, Fengrong Wang, Shreya Chalasani, Christopher J Giuliano, Sebastian Lourido, Manlio Di Cristina, Daniel J Klionsky, Vern B Carruthers","doi":"10.1080/27694127.2024.2418256","DOIUrl":"10.1080/27694127.2024.2418256","url":null,"abstract":"<p><p><i>Toxoplasma gondii</i> is a ubiquitous protozoan parasite that can reside long-term within hosts as intracellular tissue cysts comprised of chronic stage bradyzoites. To perturb chronic infection requires a better understanding of the cellular processes that mediate parasite persistence. Macroautophagy/autophagy is a catabolic and homeostatic pathway that is required for <i>T. gondii</i> chronic infection, although the molecular details of this process remain poorly understood. A key step in autophagy is the initial formation of the phagophore that sequesters cytoplasmic components and matures into a double-membraned autophagosome for delivery of the cargo to a cell's digestive organelle for degradative recycling. While <i>T. gondii</i> appears to have a reduced repertoire of autophagy proteins, it possesses a putative phospholipid scramblase, TgATG9. Through structural modeling and complementation assays, we show herein that TgATG9 can partially rescue bulk autophagy in <i>atg9Δ</i> yeast. We demonstrated the importance of TgATG9 for proper autophagosome dynamics at the subcellular level using three-dimensional live cell lattice light sheet microscopy. Conditional knockdown of TgATG9 in <i>T. gondii</i> after bradyzoite differentiation resulted in markedly reduced parasite viability. Together, our findings provide insights into the molecular dynamics of autophagosome biogenesis within an early-branching eukaryote and pinpoint the indispensable role of autophagy in maintaining <i>T. gondii</i> chronic infection.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11588310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735122","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}
Pub Date : 2024-01-01Epub Date: 2024-02-04DOI: 10.1080/27694127.2024.2305594
Jiajie Diao, Calvin K Yip, Qing Zhong
Macroautophagy (also known as autophagy) plays a pivotal role in maintaining cellular homeostasis. The terminal step of the multi-step autophagy degradation pathway involves fusion between the cargo-laden, double-membraned autophagosome and the lytic organelle lysosome/vacuole. Over the past decade, various core components of the molecular machinery that execute this critical terminal autophagy event have been identified. This review highlights recent advances in understanding the molecular structures, biochemical functions, and regulatory mechanisms of key components of this highly sophisticated machinery including the SNARE fusogens, tethering factors, Rab GTPases and associated guanine nucleotide exchange factors, and other accessory factors.
{"title":"Molecular structures and function of the autophagosome-lysosome fusion machinery.","authors":"Jiajie Diao, Calvin K Yip, Qing Zhong","doi":"10.1080/27694127.2024.2305594","DOIUrl":"10.1080/27694127.2024.2305594","url":null,"abstract":"<p><p>Macroautophagy (also known as autophagy) plays a pivotal role in maintaining cellular homeostasis. The terminal step of the multi-step autophagy degradation pathway involves fusion between the cargo-laden, double-membraned autophagosome and the lytic organelle lysosome/vacuole. Over the past decade, various core components of the molecular machinery that execute this critical terminal autophagy event have been identified. This review highlights recent advances in understanding the molecular structures, biochemical functions, and regulatory mechanisms of key components of this highly sophisticated machinery including the SNARE fusogens, tethering factors, Rab GTPases and associated guanine nucleotide exchange factors, and other accessory factors.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10852212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139725177","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}
Pub Date : 2024-01-01Epub Date: 2024-09-16DOI: 10.1080/27694127.2024.2402675
Alagie Jassey, William T Jackson
{"title":"<i>Et tu, Brute</i>? TFEB promotes virus replication before being cleaved by a viral protease.","authors":"Alagie Jassey, William T Jackson","doi":"10.1080/27694127.2024.2402675","DOIUrl":"https://doi.org/10.1080/27694127.2024.2402675","url":null,"abstract":"","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482142","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}
Pub Date : 2023-11-22DOI: 10.1080/27694127.2023.2285214
Angela Dixon, M. Shim, April Nettesheim, Aislyn Coyne, Chien-Chia Su, Haiyan Gong, P. Liton
{"title":"Autophagy deficiency protects against ocular hypertension and glaucoma","authors":"Angela Dixon, M. Shim, April Nettesheim, Aislyn Coyne, Chien-Chia Su, Haiyan Gong, P. Liton","doi":"10.1080/27694127.2023.2285214","DOIUrl":"https://doi.org/10.1080/27694127.2023.2285214","url":null,"abstract":"","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139247368","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}
Pub Date : 2023-11-14DOI: 10.1080/27694127.2023.2278946
O. Erlichman, Tamar Avin-Wittenberg
{"title":"Relative dependence: Autophagy in the mother plant and the embryo contributes to Arabidopsis seed development","authors":"O. Erlichman, Tamar Avin-Wittenberg","doi":"10.1080/27694127.2023.2278946","DOIUrl":"https://doi.org/10.1080/27694127.2023.2278946","url":null,"abstract":"","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"33 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139277162","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}
Pub Date : 2023-11-13DOI: 10.1080/27694127.2023.2277585
Pierre-Louis Tharaux, Olivia Lenoir
Pharmacological approaches aimed at increasing autophagic flux and genetically engineered mice with autophagy deficiency in the endothelium have demonstrated that autophagy exerts vessel protection against metabolic stresses and vascular aging. However, the identity of the specific cellular processes that autophagy controls in endothelial cells remained unclear. In this punctum, we discuss our recent findings on the multiple functions of autophagy in the endothelium. Particularly, we highlighted that autophagy controls flow-mediated vascular reactivity and remodeling. We have also focused on the role of autophagy machinery in regulating protein distribution within the cell and on the results demonstrating how autophagy modulates the cellular response to the microenvironment changes.
{"title":"Autophagy in the endothelium commands flow-mediated vascular reactivity and remodelling, and regulates VEGFR2 subcellular localization and signalling","authors":"Pierre-Louis Tharaux, Olivia Lenoir","doi":"10.1080/27694127.2023.2277585","DOIUrl":"https://doi.org/10.1080/27694127.2023.2277585","url":null,"abstract":"Pharmacological approaches aimed at increasing autophagic flux and genetically engineered mice with autophagy deficiency in the endothelium have demonstrated that autophagy exerts vessel protection against metabolic stresses and vascular aging. However, the identity of the specific cellular processes that autophagy controls in endothelial cells remained unclear. In this punctum, we discuss our recent findings on the multiple functions of autophagy in the endothelium. Particularly, we highlighted that autophagy controls flow-mediated vascular reactivity and remodeling. We have also focused on the role of autophagy machinery in regulating protein distribution within the cell and on the results demonstrating how autophagy modulates the cellular response to the microenvironment changes.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"38 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136347006","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}
Pub Date : 2023-11-10DOI: 10.1080/27694127.2023.2277582
Nobuo N. Noda
Atg8 and Atg12 are ubiquitin-like proteins, conjugated to phosphatidylethanolamine (PE) and Atg5, respectively, through enzymatic reactions similar to ubiquitylation. The resultant Atg8–PE and Atg12–Atg5 conjugates play crucial roles in autophagy. Structural studies have been extensively performed on all Atg proteins (Atg3, Atg4, Atg5, Atg7, Atg8, Atg10, Atg12, Atg16) involved in these conjugation systems. This review summarizes structural studies and discusses mechanisms of conjugation and deconjugation reactions, as well as autophagic functions of the Atg8 and Atg12 conjugation systems.
{"title":"Structural biology of the Atg8 and Atg12 conjugation systems","authors":"Nobuo N. Noda","doi":"10.1080/27694127.2023.2277582","DOIUrl":"https://doi.org/10.1080/27694127.2023.2277582","url":null,"abstract":"Atg8 and Atg12 are ubiquitin-like proteins, conjugated to phosphatidylethanolamine (PE) and Atg5, respectively, through enzymatic reactions similar to ubiquitylation. The resultant Atg8–PE and Atg12–Atg5 conjugates play crucial roles in autophagy. Structural studies have been extensively performed on all Atg proteins (Atg3, Atg4, Atg5, Atg7, Atg8, Atg10, Atg12, Atg16) involved in these conjugation systems. This review summarizes structural studies and discusses mechanisms of conjugation and deconjugation reactions, as well as autophagic functions of the Atg8 and Atg12 conjugation systems.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" 22","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135141882","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号