Autophagy reports最新文献_第8页

The role of autophagy in ischemic brain injury. 自噬在缺血性脑损伤中的作用。

Autophagy reports Pub Date : 2025-04-03 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2486445

Emily Osterli, Yujung Park, Kurt Hu, Gary Kasof, Thorsten Wiederhold, Chunli Liu, Bingren Hu

{"title":"The role of autophagy in ischemic brain injury.","authors":"Emily Osterli, Yujung Park, Kurt Hu, Gary Kasof, Thorsten Wiederhold, Chunli Liu, Bingren Hu","doi":"10.1080/27694127.2025.2486445","DOIUrl":"10.1080/27694127.2025.2486445","url":null,"abstract":"Ischemic brain injury occurs in many clinical settings, including stroke, cardiac arrest, hypovolemic shock, cardiac surgery, cerebral edema, and cerebral vasospasm. Decades of work have revealed many important mechanisms related to ischemic brain injury. However, there remain significant gaps in the scientific knowledge to reconcile many ischemic brain injury events. Brain ischemia leads to protein misfolding and aggregation, and damages almost all types of subcellular organelles including mitochondria, endoplasmic reticulum, Golgi apparatus, lysosomes, etc. Irreparably damaged organelles and insoluble protein aggregates are normally removed by autophagy. The build-up of common autophagic components, such as LC3, p62, and ubiquitinated proteins, are generally observed in brain tissue samples in animal models of both global and focal brain ischemia, but the interpretation of the role of these autophagy-related changes in ischemic brain injury in the literature has been controversial. Many pathological events or mechanisms underlying dysfunctional autophagy after brain ischemia remain unknown. This review aims to provide an update of the current knowledge and future research directions regarding the critical role of dysfunctional autophagy in ischemic brain injury.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2486445"},"PeriodicalIF":0.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112606","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 role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). 自噬在肌萎缩侧索硬化症（ALS）和额颞叶痴呆（FTD）的发病机制和治疗中的作用。

Autophagy reports Pub Date : 2025-03-20 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2474796

Jimmy Beckers, Philip Van Damme

{"title":"The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).","authors":"Jimmy Beckers, Philip Van Damme","doi":"10.1080/27694127.2025.2474796","DOIUrl":"10.1080/27694127.2025.2474796","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent two extremes of a neurodegenerative disease spectrum characterised by overlapping genetic, clinical, and neuropathological features. This review covers the intricate relationship between both ALS and FTD and defects in the autophagy and endolysosomal pathway as recent evidence has pointed towards alterations in these pathways as being a root cause of disease pathogenesis. Here, we review the current knowledge on the interplay between ALS/FTD and lysosomebased proteostasis pathways and carefully asses the steps of the autophagy and endolysosomal pathways that are impaired by ALS or FTDcausing variants. Finally, we present a comprehensive overview of therapeutic strategies aimed at restoring autophagic and lysosomal function as potential avenues for mitigating the impact of these devastating diseases. Through this review, we aim to enhance the understanding of the pathophysiological mechanisms involving autophagy and/or the endolysosomal system that underlie the ALS-FTD spectrum and underscore the necessity for specific therapeutic approaches that target these shared vulnerabilities.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2474796"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112683","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 machinery as exploited by viruses. 病毒利用的自噬机制。

Autophagy reports Pub Date : 2025-03-18 eCollection Date: 2025-12-31 DOI: 10.1080/27694127.2025.2464986

Christian Münz, Grant R Campbell, Audrey Esclatine, Mathias Faure, Patrick Labonte, Marion Lussignol, Anthony Orvedahl, Nihal Altan-Bonnet, Ralf Bartenschlager, Rupert Beale, Mara Cirone, Lucile Espert, Jae Jung, David Leib, Fulvio Reggiori, Sumana Sanyal, Stephen A Spector, Volker Thiel, Christophe Viret, Yu Wei, Thomas Wileman, Harald Wodrich

{"title":"Autophagy machinery as exploited by viruses.","authors":"Christian Münz, Grant R Campbell, Audrey Esclatine, Mathias Faure, Patrick Labonte, Marion Lussignol, Anthony Orvedahl, Nihal Altan-Bonnet, Ralf Bartenschlager, Rupert Beale, Mara Cirone, Lucile Espert, Jae Jung, David Leib, Fulvio Reggiori, Sumana Sanyal, Stephen A Spector, Volker Thiel, Christophe Viret, Yu Wei, Thomas Wileman, Harald Wodrich","doi":"10.1080/27694127.2025.2464986","DOIUrl":"10.1080/27694127.2025.2464986","url":null,"abstract":"Viruses adapt and modulate cellular pathways to allow their replication in host cells. The catabolic pathway of macroautophagy, for simplicity referred to as autophagy, is no exception. In this review, we discuss anti-viral functions of both autophagy and select components of the autophagy machinery, and how viruses have evaded them. Some viruses use the membrane remodeling ability of the autophagy machinery to build their replication compartments in the cytosol or efficiently egress from cells in a non-lytic fashion. Some of the autophagy machinery components and their remodeled membranes can even be found in viral particles as envelopes or single membranes around virus packages that protect them during spreading and transmission. Therefore, studies on autophagy regulation by viral infections can reveal functions of the autophagy machinery beyond lysosomal degradation of cytosolic constituents. Furthermore, they can also pinpoint molecular interactions with which the autophagy machinery can most efficiently be manipulated, and this may be relevant to develop effective disease treatments based on autophagy modulation.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813142","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

Tropheryma whipplei escapes LAPosome and modulates macrophage response in a xenophagy-dependent manner. 惠氏巨噬瘤逃逸LAPosome并以异种吞噬依赖的方式调节巨噬细胞反应。

Autophagy reports Pub Date : 2025-03-11 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2475527

Emilie Reyne, Jeffrey Arrindell, Eloïne Bestion, Soraya Mezouar, Benoit Desnues

{"title":"Tropheryma whipplei escapes LAPosome and modulates macrophage response in a xenophagy-dependent manner.","authors":"Emilie Reyne, Jeffrey Arrindell, Eloïne Bestion, Soraya Mezouar, Benoit Desnues","doi":"10.1080/27694127.2025.2475527","DOIUrl":"10.1080/27694127.2025.2475527","url":null,"abstract":"Tropheryma whipplei, the agent of Whipple's disease, is an intracellular pathogen that replicates in macrophages. The phagocytic and cellular processes leading to the formation of T. whipplei replicative vacuole remain poorly understood. Macrophage microbicidal activity is largely related to macro/autophagy which is also essential for cell homeostasis. Here, we show that T. whipplei uptake by macrophages involved LC3-associated phagocytosis (LAP). Bacteria then escaped into the cytosol from where they were recaptured by xenophagy. We also demonstrate that T. whipplei blocked the autophagic flux to build its replicative compartment. Inhibition of LAP resulted in the decrease of interleukin (IL)-10 secretion and the restoration of the autophagy flux, suggesting that modulation of autophagy during infection alters immune response and promote persistence. Our results provide new insight in the intracellular fate of the bacteria during macrophage infection and suggest the possible involvement of previously unknown virulence factors in T. whipplei infection.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2475527"},"PeriodicalIF":0.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113042","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

Evidence of the specific roles of autophagy in senescent leaves and maturing seeds. 自噬在衰老叶片和成熟种子中特定作用的证据。

Autophagy reports Pub Date : 2025-03-07 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2472160

Anne Marmagne, Fabien Chardon, Céline Masclaux-Daubresse

{"title":"Evidence of the specific roles of autophagy in senescent leaves and maturing seeds.","authors":"Anne Marmagne, Fabien Chardon, Céline Masclaux-Daubresse","doi":"10.1080/27694127.2025.2472160","DOIUrl":"10.1080/27694127.2025.2472160","url":null,"abstract":"In plants, a large part of the nutrients used to generate seed lipid and protein reserves is derived from both the degradation of macromolecules in source leaves and the transfer of small catabolic molecules like amino acids from the senescing leaves to the seeds. Studies of autophagy mutants in Arabidopsis showed that autophagy is a master player controlling 60% of the remobilization of nitrogen from senescing leaf tissues to developing seeds, and strongly impacting reserve deposition, especially in the protein to lipid ratio. Since autophagy is largely enhanced in leaves during senescence and in the seeds during maturation, we investigated the roles of autophagy in these sources and sink tissues, to identify checkpoints controlling seed filling and quality. Through gene complementation using tissue-specific promoters, we demonstrated that while autophagy regulates nitrogen flux to the seeds in source leaves, the autophagy taking place in seeds during their maturation is essential to reach the appropriate seed quality in terms of C and N storage. Overall, these results highlight the multiple roles of autophagy in the optimal development of the plant throughout its entire lifespan.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2472160"},"PeriodicalIF":0.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112208","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

Loss of nuclear envelope bud formation leads to mitophagy initiation in Drosophila muscles. 果蝇肌肉核膜芽形成缺失导致有丝分裂起始。

Autophagy reports Pub Date : 2025-03-04 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2471121

Yungui Guo, David Brooks, Ziwei Zhao, Erica Biven, Erika R Geisbrecht

{"title":"Loss of nuclear envelope bud formation leads to mitophagy initiation in Drosophila muscles.","authors":"Yungui Guo, David Brooks, Ziwei Zhao, Erica Biven, Erika R Geisbrecht","doi":"10.1080/27694127.2025.2471121","DOIUrl":"10.1080/27694127.2025.2471121","url":null,"abstract":"Pavarotti (Pav) and its binding partner Tumbleweed (Tum) are well known for their evolutionarily conserved roles in microtubule-dependent movements during cytokinesis. In post-mitotic pav RNAi muscles, we unexpectedly observed the accumulation of puncta marked by ubiquitin, p62, and Atg8a without an obvious disorganization of the microtubule network. Some of these autophagosomal structures clustered together and colocalized with mitochondria. The Pav-Tum complex was enriched in muscle nuclei, consistent with roles for Pav and Tum in nuclear envelope (NE) budding, an alternative pathway for the export of large ribonucleoproteins. One of the established cargoes of the Drosophila NE budding pathway, Marf mRNA, was indeed reduced in the myoplasm of pav RNAi muscles. Moreover, RNAi knockdown of Marf or the NE budding components Wash or Torsin also caused the clustering of p62-marked mitochondria. These data together define a model whereby blocking NE budding reduces mitochondrial activity and in turn recruits p62 and autophagic structures for a lysosomal fate.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2471121"},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112584","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

Untangling Traffic Jams: RAB11FIP4 Orchestrates Cellular Recovery in Cystinosis. 解开交通堵塞：RAB11FIP4协调胱氨酸病的细胞恢复。

Autophagy reports Pub Date : 2025-02-19 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2466121

Mouad Ait Kbaich, Jennifer L Johnson, Sergio D Catz

引用次数: 0

Role of neuronal fabp in autophagy and amyloid-β pathology in a Drosophila model of Alzheimer disease. 在阿尔茨海默病果蝇模型中，神经元fabp在自噬和淀粉样蛋白-β病理中的作用。

Autophagy reports Pub Date : 2025-02-13 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2466120

Byoungyun Choi, Kyoung Sang Cho

引用次数: 0

Glycogen is a neutral cargo of bulk autophagy in Komagataella phaffii. 糖原是法菲Komagataella phaffii大量自噬的中性货物。

Autophagy reports Pub Date : 2025-01-01 Epub Date: 2025-02-19 DOI: 10.1080/27694127.2025.2467454

Nimna V Wijewantha, Taras Y Nazarko

{"title":"Glycogen is a neutral cargo of bulk autophagy in Komagataella phaffii.","authors":"Nimna V Wijewantha, Taras Y Nazarko","doi":"10.1080/27694127.2025.2467454","DOIUrl":"10.1080/27694127.2025.2467454","url":null,"abstract":"Glycogen is a primary cellular energy store in numerous eukaryotes. Its biosynthesis is a main strategy to cope with forthcoming starvation. During starvation, glycogen is processed in the cytosol or delivered for degradation to animal lysosomes or yeast vacuoles by macroautophagy (hereafter autophagy). However, the mechanism of glycogen autophagy is poorly understood, especially in the heart and skeletal muscles that suffer from the lysosomal glycogen accumulation in Pompe disease. We recently developed the Komagataella phaffii yeast as a simple model to study glycogen autophagy and found that this pathway proceeds non-selectively. However, studies in Saccharomyces cerevisiae proposed glycogen as a non-preferred cargo of bulk autophagy. In our latest study with new fluorescent reporters for glycogen, we clarified cargo properties of K. phaffii glycogen. Both homologous and heterologous markers of glycogen are delivered to the vacuole and degraded with efficiencies that are independent of glycogen, suggesting that glycogen is a neutral cargo of bulk autophagy. This work provides insights into the evolutionary diversity of glycogen autophagy in yeasts with implications for understanding this process in complex eukaryotes.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588427","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

High throughput screening assay for the identification of ATF4 and TFEB activating compounds. ATF4和TFEB活性化合物的高通量筛选试验。

Autophagy reports Pub Date : 2025-01-01 Epub Date: 2025-04-03 DOI: 10.1080/27694127.2025.2473765

Daniel J Pfau, Ruslana Bryk

{"title":"High throughput screening assay for the identification of ATF4 and TFEB activating compounds.","authors":"Daniel J Pfau, Ruslana Bryk","doi":"10.1080/27694127.2025.2473765","DOIUrl":"10.1080/27694127.2025.2473765","url":null,"abstract":"Macrophages act to defend against infection, but can fail to completely prevent bacterial replication and dissemination in an immunocompetent host. Recent studies have shown that activation of a host transcription factor, TFEB, a regulator of lysosomal biogenesis, could restrict intramacrophage replication of the human pathogen Mycobacterium tuberculosis and synergize with suboptimal levels of the antibiotic rifampin to reduce bacterial loads. Currently available small molecule TFEB activators lack selectivity and potency, but could be potentially useful in a variety of pathological conditions with suboptimal lysosomal activity. TFEB nuclear translocation and activation depend on its phosphorylation status which is controlled by multiple cellular pathways. We devised a whole cell, high throughput screening assay to identify small molecules that activate TFEB by establishing a stably transfected HEK293T reporter cell line for ATF4, a basic leucine zipper transcription factor induced by stress response and activated in parallel to TFEB. We optimized its use in vitro using compounds that target endoplasmic reticulum stress and intracellular calcium signaling. We report results from screening the commercially available LOPAC library and the Selleck Chemicals library modified to include only FDA-approved drugs and clinical research compounds. We identified twenty-one compounds across six clinical use categories that activate ATF4, and confirmed that two proteasome inhibitors promote TFEB activation. The results of this study provide an assay that could be used to screen for small molecules that activate ATF4 and TFEB and a potential list of compounds identified as activators of the ATF4 transcription factor in response to cellular stress.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050966","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