Autophagy reports最新文献_第7页

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

Autophagy in alzheimer disease pathogenesis and its therapeutic values. 自噬在阿尔茨海默病发病机制中的作用及其治疗价值。

Autophagy reports Pub Date : 2025-05-08 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2471677

Gabrielle Angst, Nuo Jia, Luis E Tron Esqueda, Yanbo Fan, Qian Cai, Chenran Wang

{"title":"Autophagy in alzheimer disease pathogenesis and its therapeutic values.","authors":"Gabrielle Angst, Nuo Jia, Luis E Tron Esqueda, Yanbo Fan, Qian Cai, Chenran Wang","doi":"10.1080/27694127.2025.2471677","DOIUrl":"10.1080/27694127.2025.2471677","url":null,"abstract":"Alzheimer disease (AD) is the most common form of dementia with hallmarks of β-amyloid deposits, neurofilament tangles, synaptic loss and neuronal death in the patient's brain. AD is a heavy burden in an ageing society as there are no effective therapies in treating the causes or slowing down its progression. Autophagy is a conserved process through formation of double membrane structure, namely autophagosome which is delivered to lysosome to digest cellular disposals. Autophagy maintains homoeostasis in the brain and is generally considered to protect brain functions against ageing. The first evidence of autophagy involvement in AD is that there is decreased expression of autophagy essential genes in post-mortem AD brains. Autophagy is also believed to be protective in neurodegeneration. However, the molecular and cellular mechanisms for dysfunction of autophagy in AD are not fully understood. Recent studies of autophagy regulation in AD cover the findings not only in neurons, but also from fast growing evidence for their importance in glia and brain vascular system. Thus, this review composes pertinent information regarding the involvement of autophagy in neurons, glias (including microglia, astrocyte, and oligodendrocyte), and brain vascular cells in AD, and their unique cellular mechanisms of this connection in AD pathology. We will provide effectual insights both in investigating autophagy in AD pathological mechanisms and in establishing a strategic approach for developing autophagy-based AD therapies.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2471677"},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111503","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

Amino acid storage: lysosomal double role in health and disease. 氨基酸储存：溶酶体在健康和疾病中的双重作用。

Autophagy reports Pub Date : 2025-05-08 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2498324

Aiswarya Raj, Samantha Shrihari, Urmi Bandyopadhyay

{"title":"Amino acid storage: lysosomal double role in health and disease.","authors":"Aiswarya Raj, Samantha Shrihari, Urmi Bandyopadhyay","doi":"10.1080/27694127.2025.2498324","DOIUrl":"10.1080/27694127.2025.2498324","url":null,"abstract":"Cellular homeostasis depends on a multitude of cellular functions, which in turn depend on the clearance of damaged components for their maintenance. Lysosomes being one of the main sites of recycling, are at the frontline for cellular protein degradation, which leads to generation of protein building blocks, the amino acids (AAs), within the lysosomal lumen. However, the fate of these lysosomal pool of AAs are only partly known. Recently, studies from our and other groups have led to the finding that AA can be stored in lysosomes and revealed a homeostatic communication of these storages with the environment. Thus, lysosome appear to be a nutritional signaling hub that has a dual role. As a degradation-competent hydrolytic sack, lysosomes have a long-studied degradative function, additionally now they can either store or channel into utilization of the AAs generated through their proteolytic activity. Since the existence of a lysosomal AA storage pool has been determined by changing the levels of extracellular AAs, this indicates a multi-directional homeostatic communication between the lysosome and the extracellular environment. This Lysosomal homeostatic and adaptive response to the niche could be vital for life-threatening age-related degenerative disorders, where the lysosome-autophagy pathway and the microenvironmental cues play major roles in the disease progression, which will be discussed further in this piece.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2498324"},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113047","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

BECLIN-1 is essential for the maintenance of gastrointestinal epithelial integrity by regulating endocytic trafficking, F-actin organization, and lysosomal function. BECLIN-1通过调节内吞运输、f -肌动蛋白组织和溶酶体功能，对维持胃肠道上皮完整性至关重要。

Autophagy reports Pub Date : 2025-04-03 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2484494

Juliani Juliani, Sharon Tran, Tiffany J Harris, Peter De Cruz, Sarah L Ellis, Paul A Gleeson, John M Mariadason, Kinga Duszyc, Alpha S Yap, Erinna F Lee, Walter D Fairlie

{"title":"BECLIN-1 is essential for the maintenance of gastrointestinal epithelial integrity by regulating endocytic trafficking, F-actin organization, and lysosomal function.","authors":"Juliani Juliani, Sharon Tran, Tiffany J Harris, Peter De Cruz, Sarah L Ellis, Paul A Gleeson, John M Mariadason, Kinga Duszyc, Alpha S Yap, Erinna F Lee, Walter D Fairlie","doi":"10.1080/27694127.2025.2484494","DOIUrl":"10.1080/27694127.2025.2484494","url":null,"abstract":"Disrupted intestinal homeostasis and barrier function contribute to the development of diseases such as inflammatory bowel disease. BECLIN-1, a core component of two class III phosphatidylinositol 3 kinase complexes, has a dual role in autophagy and endocytic trafficking. Emerging evidence suggests that its endocytic trafficking function is essential for intestinal integrity. To investigate the fatal gastrointestinal phenotype observed in BECLIN-1 knockout mice, we used organoids derived from these animals to show that BECLIN-1 deletion disrupts the localization of CADHERIN1/ECADHERIN to adherens junctions and OCCLUDIN to tight junctions. Impaired cargo trafficking to the lysosome was also observed. Filamentous actin cytoskeleton also became disorganized though there were no changes in its spatial interaction with CATENIN BETA1/BETA-CATENIN nor in BETA-CATENIN localization. The trafficking defects were all less pronounced or absent in organoids lacking an autophagy-only regulator, ATG7, emphasizing BECLIN-1's trafficking role in maintaining gut homeostasis and barrier function. These findings advance our understanding of epithelial dysfunction and the mechanisms underlying intestinal diseases.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2484494"},"PeriodicalIF":0.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111514","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