Autophagy reports最新文献

ADP ribosylation factor-like GTPase 6-interacting protein 5 (ARL6IP5): a prenylated Rab acceptor protein 1 (PRA1) family protein that shapes the ER membrane and regulates ER-phagy. ADP核糖基化因子样GTPase 6-相互作用蛋白5 (ARL6IP5)：一个戊基化的Rab受体蛋白1 （PRA1）家族蛋白，形成内质网膜并调节内质网吞噬。

Autophagy reports Pub Date : 2025-06-10 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2513466

Yasunori Yamamoto, Toshiaki Sakisaka

{"title":"ADP ribosylation factor-like GTPase 6-interacting protein 5 (ARL6IP5): a prenylated Rab acceptor protein 1 (PRA1) family protein that shapes the ER membrane and regulates ER-phagy.","authors":"Yasunori Yamamoto, Toshiaki Sakisaka","doi":"10.1080/27694127.2025.2513466","DOIUrl":"10.1080/27694127.2025.2513466","url":null,"abstract":"The prenylated Rab acceptor protein 1 (PRA1) domain is a conserved domain encompassing four transmembrane domains (TMDs). ARL6IP5 (ADP ribosylation factor-like GTPase 6-interacting protein 5) is a member of the PRA1 family and interacts with the reticulon-homology domain (RHD)-containing proteins including ARL6IP1 (ADP ribosylation factor-like GTPase 6-interacting protein 1) and FAM134B. The RHD is a conserved domain encompassing two short hairpin TMDs and acts as a membrane-shaping unit for endoplasmic reticulum (ER) morphology and ER-phagy. However, the involvement of ARL6IP5 in ER morphology and ER-phagy remains unclear. We recently characterized ARL6IP5 as an ER membrane-shaping protein and found that ARL6IP5 constricts the ER membrane in a manner similar to ARL6IP1, possibly via short hairpin configuration of the TMDs in the PRA1 domain. ARL6IP5 also plays a redundant role with ARL6IP1 in shaping the ER membrane. Importantly, depletion of ARL6IP5 impaired FAM134B-meadited ER-phagy, which is reminiscent of ARL6IP1 depletion. These results suggested that ARL6IP5 acts as an ER membrane-shaping protein that regulates ER-phagy, underscoring the importance of the PRA1 domain. Although ARL6IP5 and ARL6IP1 are confusable protein names and seem to have similar roles in ER-phagy, we clarify in this punctum that they are distinct classes of ER membrane-shaping proteins.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2513466"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276910","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

Autophagy-enhancing strategies to promote intestinal viral resistance and mucosal barrier function in SARS-CoV-2 infection. 自噬增强策略在SARS-CoV-2感染中促进肠道病毒耐药性和粘膜屏障功能

Autophagy reports Pub Date : 2025-06-10 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2514232

Anusca G Rader, Alexandra P M Cloherty, Kharishma S Patel, Dima D A Almandawi, Jimena Perez-Vargas, Manon E Wildenberg, Vanesa Muncan, Renée R C E Schreurs, François Jean, Carla M S Ribeiro

{"title":"Autophagy-enhancing strategies to promote intestinal viral resistance and mucosal barrier function in SARS-CoV-2 infection.","authors":"Anusca G Rader, Alexandra P M Cloherty, Kharishma S Patel, Dima D A Almandawi, Jimena Perez-Vargas, Manon E Wildenberg, Vanesa Muncan, Renée R C E Schreurs, François Jean, Carla M S Ribeiro","doi":"10.1080/27694127.2025.2514232","DOIUrl":"10.1080/27694127.2025.2514232","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 19 (COVID-19), continues to circulate globally despite the widespread vaccination and therapeutics like Paxlovid, remdesivir, and molnupiravir. COVID-19 is associated with both respiratory and gastrointestinal manifestations, with persistent intestinal pathology contributing to the post-COVID-19 condition. We have previously demonstrated the antiviral activity of autophagy-blocking drugs, such as Berbamine dihydrochloride, against intestinal SARS-CoV-2 acquisition. In addition, the autophagy blockers restored the barrier function of infected intestinal epithelium. In this addendum, using human intestinal organoids, we present evidence for a protective role of intrinsic higher levels of autophagy flux in limiting intestinal SARS-CoV-2 infection. Pharmacological treatment with Akt inhibitor MK-2206 hydrochloride suppressed viral entry into the intestinal epithelium. This antiviral effect of MK-2206 was shown to be dependent on Synaptosomal-associated protein 29-dependent (SNAP-29)-mediated autophagy flux. Furthermore, extrinsically enhanced autophagy with MK-2206 also prevented SARS-CoV-2-induced intestinal barrier damage. Our findings thus underscore the intricate role of autophagy pathways in the dissemination and pathogenesis of intestinal SARS-CoV-2, highlighting the therapeutic potential of host-directed therapies targeting autophagy to intervene in COVID-19-associated sequelae and improve intestinal health.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2514232"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276911","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

Small but mighty: ATG9A-positive vesicles are a branch of the intracellular nanovesicle superfamily. 小而强大：atg9a阳性囊泡是细胞内纳米囊泡超家族的一个分支。

Autophagy reports Pub Date : 2025-06-04 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2513467

Mary Fesenko, Stephen J Royle

{"title":"Small but mighty: ATG9A-positive vesicles are a branch of the intracellular nanovesicle superfamily.","authors":"Mary Fesenko, Stephen J Royle","doi":"10.1080/27694127.2025.2513467","DOIUrl":"10.1080/27694127.2025.2513467","url":null,"abstract":"The molecular and functional characterization of the thousands of uncoated intracellular transport vesicles inside cells is a major challenge. Intracellular nanovesicles (INVs) are a large and molecularly heterogenous family of uncoated transport vesicles, which are comprised of multiple subtypes. As a step to characterizing these subtypes, we recently published the first INV proteome and were intrigued by the enrichment of ATG9A in it. ATG9A is the only conserved transmembrane protein with a core function in macroautophagy/autophagy, and it is found on small, uncoated vesicles, termed \"ATG9A-positive vesicles\". We therefore, set out to disambiguate the relationship between these two types of vesicular carriers in cells. We showed that ATG9A-containing vesicles, rather than being a distinct vesicle class, represent one subset of the INV family. We also demonstrated that this relationship is functionally important and that perturbing INV-mediated trafficking impeded starvation-induced autophagy. Here, we briefly introduce INVs, summarize the evidence supporting our definition of ATG9A-flavor INVs and present our outlook on why we hope that this classification will help to consolidate efforts to understand the functions of these vesicles in autophagy and beyond.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2513467"},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251087","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

Navigating the neuronal recycling bin: Another look at huntingtin in coordinating autophagy. 导航神经元回收箱：另一个关于亨廷顿蛋白在协调自噬中的作用。

Autophagy reports Pub Date : 2025-06-02 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2472450

Thomas J Krzystek, Shermali Gunawardena

{"title":"Navigating the neuronal recycling bin: Another look at huntingtin in coordinating autophagy.","authors":"Thomas J Krzystek, Shermali Gunawardena","doi":"10.1080/27694127.2025.2472450","DOIUrl":"10.1080/27694127.2025.2472450","url":null,"abstract":"Neurons, as post-mitotic and long-lived cells, rely heavily on autophagy to maintain cellular homoeostasis and ensure proper function. Huntingtin (HTT), a protein central to Huntington's disease (HD), has emerged as a putative multifunctional regulator within the neuronal autophagy-lysosome pathway. This review explores normal HTT's multifaceted role in neuronal autophagy, from its potential involvement in autophagy induction, its capacity to influence cargo recognition and autophagosome formation, and its contribution to autophagosome-lysosome fusion and transport. We also discuss the unique challenges that neurons face in maintaining proteostasis through autophagy, emphasising the need for specialised mechanisms like axonal transport of autophagosomes and distinct regulatory pathways. Furthermore, we highlight the spatial and temporal regulation of neuronal autophagy, particularly in the context of ageing and neuronal maturation, underscoring the importance of understanding HTT's role in different neuronal states. By elucidating the intricate relationship between HTT and neuronal autophagy, this review aims to shed light on specific mechanisms of action in autophagy that can be disrupted in neurodegenerative diseases including HD.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2472450"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236089","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

Active protein quality control in quiescence: involvement of proteasomes, autophagy, and nucleus-vacuole junctions. 静止状态下活性蛋白质量控制：蛋白酶体、自噬和核-液泡连接的参与。

Autophagy reports Pub Date : 2025-05-31 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2507266

Mihaela Pravica, Dina Franić, Mirta Boban

引用次数: 0

A plasmid module for PCR-based gene modification for the accurate measurement of vacuolar delivery of specific proteins in yeast Saccharomyces cerevisiae. 一种基于pcr的基因修饰质粒模块，用于精确测量酵母中特定蛋白质的空泡递送。

Autophagy reports Pub Date : 2025-05-31 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2511724

Jakob Valdbjørn Kanne, Fulvio Reggiori

{"title":"A plasmid module for PCR-based gene modification for the accurate measurement of vacuolar delivery of specific proteins in yeast Saccharomyces cerevisiae.","authors":"Jakob Valdbjørn Kanne, Fulvio Reggiori","doi":"10.1080/27694127.2025.2511724","DOIUrl":"10.1080/27694127.2025.2511724","url":null,"abstract":"Monitoring the delivery of single proteins and protein complexes to the vacuole by autophagy or other processes in yeast Saccharomyces cerevisiae mainly relies on western blot or fluorescence microscopy analyses using endogenous tagging of the protein of interest with GFP. However, these approaches are semi-quantitative and next to impossible with proteins of low abundancy because of the insensitive nature of the methods. Here, we describe the creation of a new PCR-based integration cassette to endogenously tag specific proteins with the truncated version of the vacuolar phosphatase Pho8. The vacuolar activation of Pho8 allows the quantitative measurement of vacuolar delivery using a colorimetric enzymatic assay. This approach has the advantages of a more quantitative interpretation of data and relies on the appearance of a signal rather than its disappearance. As a proof-of-principle, we examined the vacuolar delivery of known cargoes of bulk autophagy and endocytosis. This new system will be of great value to the whole community working within the field of autophagy and other transport pathways to the vacuole.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2511724"},"PeriodicalIF":0.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210324","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

The TECPR1:ATG5-ATG12 complex conjugates LC3/ATG8 to damaged lysosomes that expose luminal glycans in response to osmotic imbalance. TECPR1:ATG5-ATG12复合物将LC3/ATG8结合到受损的溶酶体上，这些溶酶体暴露于腔内聚糖，以响应渗透失衡。

Autophagy reports Pub Date : 2025-05-30 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2476218

Yingxue Wang, Matthew Jefferson, Maria Ramos, Matthew Whelband, Kristin Kreuzer, Grace Khuu, Michael Lazarou, James Mccoll, James Lazenby, Cynthia B Whitchurch, Paul Verkade, Ulrike Mayer, Thomas Wileman

{"title":"The TECPR1:ATG5-ATG12 complex conjugates LC3/ATG8 to damaged lysosomes that expose luminal glycans in response to osmotic imbalance.","authors":"Yingxue Wang, Matthew Jefferson, Maria Ramos, Matthew Whelband, Kristin Kreuzer, Grace Khuu, Michael Lazarou, James Mccoll, James Lazenby, Cynthia B Whitchurch, Paul Verkade, Ulrike Mayer, Thomas Wileman","doi":"10.1080/27694127.2025.2476218","DOIUrl":"10.1080/27694127.2025.2476218","url":null,"abstract":"Hydrolytic enzymes within lysosomes maintain cell and tissue homoeostasis by degrading macromolecules delivered by endocytosis and autophagy. The release of lysosomal enzymes into the cytosol can induce apoptosis and \"lysosome-dependent cell death\" making it important for damaged lysosomes to be repaired or removed. Extensive lysosome damage exposes luminal sugars to galectin-dependent autophagy pathways that use ATG16L1:ATG5-ATG12 complex to conjugate LC3/ATG8 to autophagosomes to facilitate removal by lysophagy. Sphingomyelin exposed on stressed lysosomes recruits the lysosome tethering protein TECPR1 (tectonin beta propeller repeat-containing protein) allowing an alternative TECRP1:ATG5-ATG12 complex to conjugate LC3 directly to lysosomes. Here we have used cells lacking ATG16L1 to follow the recruitment of TECPR1, galectin-3 and LC3/ATG8 to lysosomes in response to osmotic imbalance induced by chloroquine. TECPR1 was recruited to swollen lysosomes that exposed sphingomyelin. LC3II was absent from swollen lysosomes but located to small puncta that contained the V-ATPase and LAMP1. The presence of galectin-3 and PI4P in the small LC3 puncta suggested that the TECPR1:ATG5-ATG12 complex conjugates LC3 to lysosome remnants that have ruptured in response to osmotic imbalance.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2476218"},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210326","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

Identification of a novel mechanism for regulation of the early autophagy machinery assembly by PKA. 鉴定PKA调控早期自噬机制组装的新机制。

Autophagy reports Pub Date : 2025-05-11 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2503226

Miranda Bueno-Arribas, Olivier Vincent

引用次数: 0

Metamorphosis and development of malaria parasites in the liver are regulated by unconventional autophagy. 疟疾寄生虫在肝脏中的变态和发育受非常规自噬的调节。

Autophagy reports Pub Date : 2025-05-11 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2504060

Suryansh Rajput, Satish Mishra

{"title":"Metamorphosis and development of malaria parasites in the liver are regulated by unconventional autophagy.","authors":"Suryansh Rajput, Satish Mishra","doi":"10.1080/27694127.2025.2504060","DOIUrl":"10.1080/27694127.2025.2504060","url":null,"abstract":"Malaria parasites encounter diverse conditions as they transition between mosquito and mammalian hosts. A characteristic of the sporozoite stage of the parasite is that once it enters the hepatocyte, it changes its morphology and metabolism. Motile-elongated sporozoites transform into round trophozoites, discard unnecessary organelles, undergo extensive replication, and mature into hepatic merozoites. However, the mechanisms of superfluous organelle elimination and apicoplast biogenesis are unclear. In our latest study, using a conditional mutagenesis system, we clarified the role of Atg7 during parasite metamorphosis in the liver. We found that cytosolic Atg7 is essential for the localization of Atg8 on the membrane and the development of parasites in the blood and liver stages. Parasites lacking Atg7 fail to lipidate Atg8 on the membrane, which leads to impaired exocytosis of micronemes, and parasites eventually fail to mature into hepatic merozoites. This work provides insights into the essential role of Atg7 in maintaining parasite cellular homeostasis during liver stage development.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2504060"},"PeriodicalIF":0.0,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112592","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

A new role of RAB21 and VARP in autophagy and autophagic exocytosis of ATP. RAB21和VARP在ATP自噬和自噬胞吐中的新作用。

Autophagy reports Pub Date : 2025-05-11 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2501365

María Carolina Barbosa, Pablo Reta, Sébastien Nola, Milton Osmar Aguilera, Thierry Galli, María Isabel Colombo, Claudio Marcelo Fader

{"title":"A new role of RAB21 and VARP in autophagy and autophagic exocytosis of ATP.","authors":"María Carolina Barbosa, Pablo Reta, Sébastien Nola, Milton Osmar Aguilera, Thierry Galli, María Isabel Colombo, Claudio Marcelo Fader","doi":"10.1080/27694127.2025.2501365","DOIUrl":"10.1080/27694127.2025.2501365","url":null,"abstract":"Autophagy has been implicated in various cellular processes, including non-conventional secretion. Our previous findings suggest that ATP is loaded into amphisomes and secreted upon autophagy stimulation at focal adhesion sites in a VAMP7-dependent manner. Here, we demonstrate that the knockout (KO) of VAMP7, along with its partners RAB21 and its guanine nucleotide exchange factor (GEF) VARP, inhibits ATP release, indicating a key role for this pathway in amphisome secretion. Constitutively inactive RAB21 also inhibited ATP secretion. RAB21 overexpression rescued starvation-induced ATP secretion in RAB21 KO, but not in VAMP7 or VARP KO cells. RAB21-LC3-positive vesicles redistributed to the cell periphery upon starvation. KO cells and overexpression experiments showed that RAB21 plays a positive role in autophagosome biogenesis, particularly in controlling the number of LC3-II- and DFCP1-positive structures upon starvation, suggesting a role in the early steps of autophagosome formation. Accordingly, VARP partially colocalized with LC3 upon starvation. Together, these findings identify a novel role for RAB21 in regulating autophagic ATP secretion likely in amphisome biogenesis and their localization in the cell periphery.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2501365"},"PeriodicalIF":0.0,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113044","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