Autophagy reports最新文献_第9页

The Role of Autophagy in Excitotoxicity, Synaptic Mitochondrial Stress and Neurodegeneration. 自噬在兴奋毒性、突触线粒体应激和神经退行性变中的作用

Autophagy reports Pub Date : 2025-01-01 Epub Date: 2025-03-10 DOI: 10.1080/27694127.2025.2464376

Charleen T Chu

{"title":"The Role of Autophagy in Excitotoxicity, Synaptic Mitochondrial Stress and Neurodegeneration.","authors":"Charleen T Chu","doi":"10.1080/27694127.2025.2464376","DOIUrl":"10.1080/27694127.2025.2464376","url":null,"abstract":"Brain and nervous system functions depend upon maintaining the integrity of synaptic structures over the lifetime. Autophagy, a key homeostatic quality control system, plays a central role not only in neuronal development and survival/cell death, but also in regulating synaptic activity and plasticity. Glutamate is the major excitatory neurotransmitter that activates downstream targets, with a key role in learning and memory. However, an excess of glutamatergic stimulation is pathological in stroke, epilepsy and neurodegeneration, triggering excitotoxic cell death or a sublethal process of excitatory mitochondrial calcium toxicity (EMT) that triggers dendritic retraction. Markers of autophagy and mitophagy are often elevated following excitatory neuronal injuries, with the potential to influence cell death or neurodegenerative outcomes of these injuries. Interestingly, leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced kinase 1 (PINK1), two kinases linked to autophagy, mitophagy and Parkinson disease, play important roles in regulating mitochondrial calcium handling, synaptic density and function, and maturation of dendritic spines. Mutations in LRRK2, PINK1, or proteins linked to Alzheimer's disease perturb mitochondrial calcium handling to sensitize neurons to excitatory injury. While autophagy and mitophagy can play both protective and harmful roles, studies in various excitotoxicity and stroke models often implicate autophagy in a pathogenic role. Understanding the role of autophagic degradation in regulating synaptic loss and cell death following excitatory neuronal injuries has important therapeutic implications for both acute and chronic neurological disorders.","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/PMC11921967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797196","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

Image-based temporal profiling of autophagy-related phenotypes. 自噬相关表型的基于图像的时间分析。

Autophagy reports Pub Date : 2025-01-01 Epub Date: 2025-04-08 DOI: 10.1080/27694127.2025.2484835

Nitin Sai Beesabathuni, Neil Alvin B Adia, Eshan Thilakaratne, Ritika Gangaraju, Priya S Shah

{"title":"Image-based temporal profiling of autophagy-related phenotypes.","authors":"Nitin Sai Beesabathuni, Neil Alvin B Adia, Eshan Thilakaratne, Ritika Gangaraju, Priya S Shah","doi":"10.1080/27694127.2025.2484835","DOIUrl":"10.1080/27694127.2025.2484835","url":null,"abstract":"Autophagy is a dynamic process critical in maintaining cellular homoeostasis. Dysregulation of autophagy is linked to many diseases and is emerging as a promising therapeutic target. High-throughput methods to characterise autophagy are essential for accelerating drug discovery and characterising mechanisms of action. In this study, we developed a scalable image-based temporal profiling approach to characterise ~900 morphological features at a single cell level with high temporal resolution. We differentiated drug treatments based on morphological profiles using a random forest classifier with ~90% accuracy and identified the key features that govern classification. Additionally, temporal morphological profiles accurately predicted biologically relevant changes in autophagy after perturbation, such as total cargo degraded. Therefore, this study acts as proof-of-principle for using image-based temporal profiling to differentiate autophagy perturbations in a high-throughput manner and has the potential identify biologically relevant autophagy phenotypes. Ultimately, approaches like image-based temporal profiling can accelerate drug discovery.","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/PMC11988254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059110","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

Positional specialization of LIR motifs in RavZ and the autophagy-related protein ATG4B. LIR基序在RavZ和自噬相关蛋白ATG4B中的位置特化。

Autophagy reports Pub Date : 2024-12-19 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2024.2438563

Sang-Won Park, Jin-A Lee, Deok-Jin Jang

引用次数: 0

Mechanistic insights into the interaction between optineurin with RAB8A. opopineurin与RAB8A相互作用机制的研究。

Autophagy reports Pub Date : 2024-12-05 eCollection Date: 2024-01-01 DOI: 10.1080/27694127.2024.2432848

Jing Zhang, Lifeng Pan

引用次数: 0

NLRP4 drives olaparib resistance in pancreatic cancer. NLRP4驱动胰腺癌的奥拉帕尼耐药

Autophagy reports Pub Date : 2024-12-02 eCollection Date: 2024-01-01 DOI: 10.1080/27694127.2024.2422729

Mingming Xiao, Xianjun Yu, Si Shi

{"title":"NLRP4 drives olaparib resistance in pancreatic cancer.","authors":"Mingming Xiao, Xianjun Yu, Si Shi","doi":"10.1080/27694127.2024.2422729","DOIUrl":"10.1080/27694127.2024.2422729","url":null,"abstract":"Olaparib has been approved as a treatment for metastatic pancreatic ductal adenocarcinoma in patients with BRCA1 (BRCA1 DNA repair associated) or BRCA2 mutations. However, a large portion of pancreatic cancer patients either exhibit inherent resistance or develop resistance over time. Understanding the molecular mechanisms that drive this resistance is crucial to develop more effective targeted therapies. In this study, we found that NLRP4 (NLR family pyrin domain containing 4) upregulation is associated with increased resistance to olaparib in pancreatic cancer. In addition, NLRP4 plays a role in both the DNA damage response (DDR) and autophagy. Specifically, NLRP4 enhances DNA repair capacity and leads to increased reactive oxygen species (ROS) production and autophagy upon olaparib treatment. Notably, NLRP4-generated mitochondrial ROS promote autophagy without directly impacting DNA damage. Inhibition of either mitochondrial ROS production with MitoQ or autophagy with chloroquine (CQ) could sensitize pancreatic cancer cells to olaparib. These findings emphasize NLRP4's role in promoting both autophagy and DNA repair in response to olaparib, suggesting that patients with low NLRP4 expression might respond more favorably to olaparib treatment.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"3 1","pages":"2422729"},"PeriodicalIF":0.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113021","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

Co-opted ATG2 lipid transfer protein delivers phospholipids for biogenesis of viral replication organelles. 增选ATG2脂质转移蛋白为病毒复制细胞器的生物发生提供磷脂。

Autophagy reports Pub Date : 2024-12-01 eCollection Date: 2024-01-01 DOI: 10.1080/27694127.2024.2426437

Yuanrong Kang, Judit Pogany, Peter D Nagy

引用次数: 0

PINK1/PARKIN-mediated mitophagy inhibits the interferon response and promotes viral replication during Pseudorabies virus infection. 在伪狂犬病毒感染期间，PINK1/ parkin介导的线粒体自噬抑制干扰素反应并促进病毒复制。

Autophagy reports Pub Date : 2024-11-27 eCollection Date: 2024-01-01 DOI: 10.1080/27694127.2024.2422214

Yuan Zhao, Zhenbang Zhu, Wenqiang Wang, Zhendong Zhang, Wei Wen, Xiangdong Li

引用次数: 0

Chaperone-mediated autophagy in fish: A key function amid a changing environment. 伴侣介导的自噬在鱼类：一个关键功能在不断变化的环境。

Autophagy reports Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.1080/27694127.2024.2403956

Simon Schnebert, Emilio J Vélez, Maxime Goguet, Karine Dias, Vincent Véron, Isabel García-Pérez, Lisa M Radler, Emilie Cardona, Stéphanie Fontagné-Dicharry, Pierre Van Delft, Franziska Dittrich-Domergue, Amélie Bernard, Florian Beaumatin, Amaury Herpin, Beth Cleveland, Iban Seiliez

{"title":"Chaperone-mediated autophagy in fish: A key function amid a changing environment.","authors":"Simon Schnebert, Emilio J Vélez, Maxime Goguet, Karine Dias, Vincent Véron, Isabel García-Pérez, Lisa M Radler, Emilie Cardona, Stéphanie Fontagné-Dicharry, Pierre Van Delft, Franziska Dittrich-Domergue, Amélie Bernard, Florian Beaumatin, Amaury Herpin, Beth Cleveland, Iban Seiliez","doi":"10.1080/27694127.2024.2403956","DOIUrl":"10.1080/27694127.2024.2403956","url":null,"abstract":"Chaperone-Mediated Autophagy (CMA) is a major pathway of lysosomal proteolysis critical for cellular homoeostasis and metabolism. While extensively studied in mammals, CMA's existence in fish has only been confirmed recently, offering exciting insights into its role in species facing environmental stress. Here, we shed light on the existence of 2 genes encoding the CMA-limiting factor Lamp2A (lysosomal associated membrane protein 2A) in rainbow trout (RT, Oncorhynchus mykiss), revealing distinct expression patterns across various tissues. Notably, RT lacking the most expressed Lamp2A exhibit profound hepatic proteome disturbances during acute nutritional stress, underscoring its pivotal role as a guardian of hepatic proteostasis. Building upon these findings, we introduce and validate the CMA activation score as a reliable indicator of CMA status, providing a valuable tool for detecting cellular stress in fish under environmental threats. Overall, our study offers new perspectives into understanding CMA from evolutionary and environmental contexts.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"3 1","pages":"2403956"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112953","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 plants. 植物中的自噬。

Autophagy reports Pub Date : 2024-10-15 eCollection Date: 2024-01-01 DOI: 10.1080/27694127.2024.2395731

Morten Petersen, Tamar Avin-Wittenberg, Diane C Bassham, Yasin Dagdas, Chudi Fan, Alisdair R Fernie, Liwen Jiang, Divya Mishra, Marisa S Otegui, Eleazar Rodriguez, Daniel Hofius

{"title":"Autophagy in plants.","authors":"Morten Petersen, Tamar Avin-Wittenberg, Diane C Bassham, Yasin Dagdas, Chudi Fan, Alisdair R Fernie, Liwen Jiang, Divya Mishra, Marisa S Otegui, Eleazar Rodriguez, Daniel Hofius","doi":"10.1080/27694127.2024.2395731","DOIUrl":"10.1080/27694127.2024.2395731","url":null,"abstract":"Autophagy is a process of cellular self-eating, which allows organisms to eliminate and recycle unwanted components and damaged organelles to maintain cellular homeostasis. It is an important process in the development of eukaryotic organisms. Autophagy plays a critical role in many physiological processes in plants such as nutrient remobilization, cell death, immunity, and abiotic stress responses. Autophagy thus represents an obvious target for generating resilient crops. During plant development, autophagy is also implicated in the differentiation and maturation of various cell types and plant organs, including root cap cells, tracheary elements, gametes, fruits and seeds. Here, we review our current understanding and recent advances of plant autophagy including insight into autophagy regulation and signaling as well as autophagosome membrane biogenesis. In addition, we describe how autophagy contributes to development, metabolism, biotic and abiotic stress tolerance and where the autophagic field is heading in terms of applied research for crop improvement.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"3 1","pages":"2395731"},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112935","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

ATG5 is dispensable for ATG8ylation of cellular proteins. ATG5对于细胞蛋白的atg8化是不可缺少的。

Autophagy reports Pub Date : 2024-10-12 eCollection Date: 2024-01-01 DOI: 10.1080/27694127.2024.2392450

Robin Ketteler, Koshiro Kiso, Lucas von Chamier, Alexander Agrotis

{"title":"ATG5 is dispensable for ATG8ylation of cellular proteins.","authors":"Robin Ketteler, Koshiro Kiso, Lucas von Chamier, Alexander Agrotis","doi":"10.1080/27694127.2024.2392450","DOIUrl":"10.1080/27694127.2024.2392450","url":null,"abstract":"Protein ATG8ylation refers to a post-translational modification involving covalent attachment of ubiquitin-like autophagy-related protein ATG8 (LC3/GABARAP) to other cellular proteins, with reversal mediated by ATG4 proteases. While lipid ATG8ylation is important for autophagosome formation and mechanistically well-characterized, little is known about the mechanism of protein ATG8ylation. Here, we investigated the conjugation machinery of protein ATG8ylation in CRISPR/Cas9-engineered knockout human cell lines, utilizing a deconjugation-resistant (Q116P G120) form of MAP1LC3B. We report that protein ATG8ylation requires the E1-like activating enzyme ATG7 and E2-like conjugating enzyme ATG3, in common with ATG8 lipidation. However, in contrast, the E3-like ATG12-ATG5-ATG16L1 complex involved in lipidation is dispensable for protein ATG8ylation, since ATG5 knockout cells can form ATG8ylated protein conjugates. Further, we uncover that ATG7 itself is a target of ATG8ylation. Overall, our work provides crucial insight into the mechanism of protein ATG8ylation, distinguishing it from ATG8 lipidation, which will aid investigating its functional role.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"3 1","pages":"2392450"},"PeriodicalIF":0.0,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112929","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