Autophagy reports最新文献_第3页

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

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":"https://doi.org/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