Autophagy最新文献_第2页

Unraveling the Link between Class 1A PI3-Kinase, Autophagy, and Myelodysplasia. 揭示 1A 级 PI3-激酶、自噬与骨髓增生异常之间的联系

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-06-12 DOI: 10.1080/15548627.2023.2221922

Kristina Ames, Kira Gritsman

引用次数: 0

Inhibiting autophagy before it starts. 在自噬开始之前就加以抑制

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-04-10 DOI: 10.1080/15548627.2023.2197364

Yuqi Lin, Biao Yu, Pengfei Fang, Jing Wang

{"title":"Inhibiting autophagy before it starts.","authors":"Yuqi Lin, Biao Yu, Pengfei Fang, Jing Wang","doi":"10.1080/15548627.2023.2197364","DOIUrl":"10.1080/15548627.2023.2197364","url":null,"abstract":"Autophagy, an important cellular stress response mechanism, is often exploited by a variety of cancer cells to sustain rapid growth under stresses such as nutrient deprivation and hypoxia. Autophagy also plays a key role in tumor resistance to chemotherapy, radiotherapy or targeted therapy. Inhibition of autophagy is therefore a promising tumor treatment strategy. However, there is still a lack of effective autophagy inhibitors suitable for clinical use. Most drug development has focused on enzymes like the VPS34 and ULK1 kinases, or the cysteine protease ATG4B, which plays different roles in autophagy. We discovered a drug molecule Eltrombopag that inhibits the expression of autophagic lysosomal genes at the stage of transcriptional level, where the synthesis of these proteins has not really begun, by directly inhibiting the TFEB (transcription factor EB). This drug can improve the therapeutic effect of Temozolomide on glioblastoma treatment, further confirming the value of inhibiting autophagy in the treatment of cancer.Abbreviation: VPS34: vacuolar protein sorting 34; ULK1: unc-51 like autophagy activating kinase 1; TFEB: transcription factor EB; MITF: microphthalmia-associated transcription factor; TFE3: transcription factor E3; EO: Eltrombopag; ITC: isothermal titration calorimetry; bHLH-LZ: basic helix-loop-helix leucine zipper; LAMP1: lysosomal-associated membrane protein 1; CTSF: cathepsin F; HEXA: hexosaminidase subunit alpha.","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"923-924"},"PeriodicalIF":14.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9264542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From jeopardy champion to drug discovery; semantic similarity artificial intelligence. 从危险冠军到药物发现；语义相似性人工智能。

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-05-14 DOI: 10.1080/15548627.2023.2210995

Natalia Moskal, G Angus McQuibban

{"title":"From jeopardy champion to drug discovery; semantic similarity artificial intelligence.","authors":"Natalia Moskal, G Angus McQuibban","doi":"10.1080/15548627.2023.2210995","DOIUrl":"10.1080/15548627.2023.2210995","url":null,"abstract":"We have employed artificial intelligence to streamline the small molecule drug screening pipeline and identified the cholesterol-reducing compound probucol in the process. Probucol augmented mitophagy and prevented loss of dopaminergic neurons in flies and zebrafish challenged with mitochondrial toxins. Further dissection of the mechanism of action led to the identification of ABCA1, the target of probucol, as a mitophagy modulator. Probucol treatment regulates lipid droplet dynamics during mitophagy and ABCA1 is required for these effects. Here we will summarize the combination of in silico and cell-based screening that led us to identify and characterize probucol as a compound that enhances mitophagy and include thoughts about future directions for the topics explored in our study.Abbreviations: ABCA1: ATP binding cassette transporter protein 1; ATP: Adenosine tri-phosphate; CCCP: carbonyl cyanide m-chlorophenylhydrazone; DsRed: Discosoma red; FDA: Food and drug administration; GFP: Green fluorescent protein; LAMP: lysosome-associated membrane glycoproteins; LD: Lipid droplet; PD: Parkinson's disease; PINK: PTEN-induced kinase.","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"935-937"},"PeriodicalIF":14.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9453523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","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-dependent expression of osteopontin and its downstream Stat3 signaling contributes to lymphatic malformation progression to lymphangiosarcoma. 依赖于自噬的骨化素表达及其下游 Stat3 信号传导有助于淋巴畸形发展为淋巴管肉瘤。

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-05-14 DOI: 10.1080/15548627.2023.2213527

Fuchun Yang, Jun-Lin Guan

{"title":"Autophagy-dependent expression of osteopontin and its downstream Stat3 signaling contributes to lymphatic malformation progression to lymphangiosarcoma.","authors":"Fuchun Yang, Jun-Lin Guan","doi":"10.1080/15548627.2023.2213527","DOIUrl":"10.1080/15548627.2023.2213527","url":null,"abstract":"Lymphatic malformation (LM) is a vascular anomaly from lymphatic endothelial cells (ECs), and a fraction of the patients could progress to the deadly malignant lymphangiosarcoma (LAS). Using genetic tools to delete an essential autophagy gene Rb1cc1/FIP200 or its mutation specifically blocking its autophagy function, we demonstrated that autophagy inhibition abrogated LM progression to LAS although not affecting LM formation in our recently developed mouse model of LAS. Analysis of the mouse models in vivo and vascular tumor cells in vitro showed that autophagy inhibition reduced vascular tumor cell proliferation in vitro and tumorigenicity in vivo without affecting mTORC1 signaling as an oncogenic driver directly. Transcriptional profiling of autophagy-deficient tumor cells and further mechanistic studies revealed a role for osteopontin (OPN) and its downstream Jak/Stat3 signaling in mediating regulation of vascular tumor cells by autophagy. Together, these results support potential new prophylactic strategies to targeting autophagy and/or its downstream OPN expression to prevent progression of the benign LM to the malignant and deadly LAS.Abbreviations: LM: lymphatic malformation; EC: endothelial cell; LAS: lymphangiosarcoma; OPN: osteopontin; RB1CC1: RB1 Inducible Coiled-Coil 1; FIP200: FAK family-interacting protein of 200 kDa.","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"941-942"},"PeriodicalIF":14.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9508184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BAX/MLKL signaling contributes to lipotoxicity-induced lysosomal membrane permeabilization in alcohol-associated liver disease. 在酒精相关性肝病中，BAX/MLKL 信号传导有助于脂肪毒性诱导的溶酶体膜通透性。

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-06-13 DOI: 10.1080/15548627.2023.2221989

Haibo Dong, Wei Guo, Zhanxiang Zhou

{"title":"BAX/MLKL signaling contributes to lipotoxicity-induced lysosomal membrane permeabilization in alcohol-associated liver disease.","authors":"Haibo Dong, Wei Guo, Zhanxiang Zhou","doi":"10.1080/15548627.2023.2221989","DOIUrl":"10.1080/15548627.2023.2221989","url":null,"abstract":"Lysosomal membrane permeabilization (LMP) has emerged as a significant component of cellular signaling pathway by which autophagy or cell death is regulated under many pathological situations including alcohol-associated liver disease (ALD). However, the mechanisms involved in the regulation of LMP in ALD remain obscure. Recently, we demonstrated that lipotoxicity serves as a causal factor to trigger LMP in hepatocytes. We identified that the apoptotic protein BAX (BCL2 associated X, apoptosis regulator) could recruit MLKL (mixed lineage kinase domain-like pseudokinase), a necroptotic executive protein, to lysosomes and induce LMP in various ALD models. Importantly, the pharmacological or genetic inhibition of BAX or MLKL protects hepatocytes from lipotoxicity-induced LMP. Thus, our study reveals a novel molecular mechanism that activation of BAX/MLKL signaling contributes to the pathogenesis of ALD through mediating lipotoxicity-induced LMP.Abbreviations: ALD: alcohol-associated liver disease; BAX: BCL2 associated X; LAMP2: lysosomal associated membrane protein 2; LMP: lysosomal membrane permeabilization; MLKL: mixed lineage kinase domain-like pseudokinase; PA: palmitic acid.","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"958-959"},"PeriodicalIF":14.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9616566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

STING recruits WIPI2 for autophagosome formation. STING 为自噬体的形成招募 WIPI2。

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-04-13 DOI: 10.1080/15548627.2023.2202108

Wei Wan, Wei Liu

{"title":"STING recruits WIPI2 for autophagosome formation.","authors":"Wei Wan, Wei Liu","doi":"10.1080/15548627.2023.2202108","DOIUrl":"10.1080/15548627.2023.2202108","url":null,"abstract":"Induction of autophagy is a primordial function of the cGAS-STING pathway. However, the molecular mechanisms regulating autophagosome formation during STING-induced autophagy remain largely unknown. Recently, we reported that STING directly interacts with WIPI2 to recruit WIPI2 onto STING-positive vesicles for LC3 lipidation and autophagosome formation. We found that STING and PtdIns3P competitively bind to the FRRG motif of WIPI2, resulting in a mutual inhibition between STING-induced and PtdIns3P-dependent autophagy. We also showed that STING-WIPI2 interaction is necessary for cells to clear cytoplasmic DNA and attenuate activated cGAS-STING signaling. In summary, by identifying the interaction between STING and WIPI2, our study revealed a mechanism that allows STING to bypass the canonical upstream machinery to induce autophagosome formation.Abbreviations: ATG: autophagy-related; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; cGAMP: cyclic GMP-AMP; cGAS: cyclic GMP-AMP synthase; ER: endoplasmic reticulum; ERGIC: ER-Golgi intermediate compartment; IRF3: interferon regulatory factor 3; PtdIns3P: phosphatidylinositol-3-phosphate; SQSTM1: sequestosome 1; STING: stimulator of interferon genes; TBK1: TANK-binding kinase 1; ULK1: unc-51 like autophagy activating kinase 1; WIPI2: WD repeat domain, phosphoinositide interacting 2.","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"928-929"},"PeriodicalIF":14.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9286046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","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 paradigm shift: AMPK negatively regulates ULK1 activity. 范式转变：AMPK 负向调节 ULK1 的活性。

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-06-20 DOI: 10.1080/15548627.2023.2223465

Ji-Man Park, Do-Hyung Kim

{"title":"A paradigm shift: AMPK negatively regulates ULK1 activity.","authors":"Ji-Man Park, Do-Hyung Kim","doi":"10.1080/15548627.2023.2223465","DOIUrl":"10.1080/15548627.2023.2223465","url":null,"abstract":"In glucose-starved cells, macroautophagy (hereafter referred to as autophagy) is considered to serve as an energy-generating process contributing to cell survival. AMPK (adenosine monophosphate-activated protein kinase) is the primary cellular energy sensor that is activated during glucose starvation. According to the current paradigm in the field, AMPK promotes autophagy in response to energy deprivation by binding and phosphorylating ULK1 (UNC-51 like kinase 1), the protein kinase responsible for autophagy initiation. However, conflicting findings have been reported casting doubts about the current established model. In our recent study, we have thoroughly reevaluated the role of AMPK in autophagy. Contrary to the current paradigm, our study revealed that AMPK functions as a negative regulator of ULK1 activity. The study has elucidated the underlying mechanism and demonstrated the significance of the negative role in controlling autophagy and maintaining cellular resilience during energy depletion.Abbreviations: AMPK: adenosine monophosphate-activated protein kinase; ULK1: UNC-51 like kinase 1; MTORC1: mechanistic target of rapamycin complex 1; ATG14: autophagy-related protein 14; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; ATP: adenosine triphosphate; VPS34: vacuolar protein sorting 34; BECN1: Beclin 1; AMPKα: AMPK catalytic subunit α; LKB1: liver kinase B1; PIK3R4: phosphatidylinositol 3-kinase regulatory subunit 4.","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"960-962"},"PeriodicalIF":14.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10042888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An emerging role of non-canonical conjugation of ATG8 proteins in plant response to heat stress. ATG8 蛋白的非典型共轭作用在植物应对热胁迫中的新作用。

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-05-31 DOI: 10.1080/15548627.2023.2219161

Xuanang Zheng, Siyu Chen, Caiji Gao, Jun Zhou

{"title":"An emerging role of non-canonical conjugation of ATG8 proteins in plant response to heat stress.","authors":"Xuanang Zheng, Siyu Chen, Caiji Gao, Jun Zhou","doi":"10.1080/15548627.2023.2219161","DOIUrl":"10.1080/15548627.2023.2219161","url":null,"abstract":"Members of the ATG8 (autophagy-related protein 8) protein family can be non-canonically conjugated to single membrane-bound organelles. The exact function of ATG8 on these single membranes remains poorly understood. Recently, using Arabidopsis thaliana as a model system, we identified a non-canonical conjugation of ATG8 pathway involved in the reconstruction of the Golgi apparatus upon heat stress. Short acute heat stress resulted in rapid vesiculation of the Golgi, which was accompanied with the translocation of ATG8 proteins (ATG8a to ATG8i) to the dilated cisternae. More importantly, we found that ATG8 proteins can recruit clathrin to facilitate Golgi reassembly by stimulating the budding of ATG8-positive vesicles from dilated cisternae. These findings provide new insight into one of the possible functions of ATG8 translocation onto single membrane organelles, and will contribute to a better understanding of non-canonical conjugation of ATG8 in eukaryotic cells.Abbreviations: ADS, AIMs docking site; AIM, ATG8-interacting motif; ATG, autophagy-related; CLC2, Clathrin light chain 2; ConcA, concanamycin A; HS, heat stress; PE, phosphatidylethanolamine; PM, plasma membrane; PS, phosphatidylserine; TGN, trans-Golgi network; V-ATPase, vacuolar-type ATPase.","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"946-948"},"PeriodicalIF":14.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9545950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metamorphosis by ATG13 and ATG101 in human autophagy initiation. ATG13 和 ATG101 在人类自噬启动过程中的变态反应

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-07-02 DOI: 10.1080/15548627.2023.2230054

Anoshi Patel, Alex C Faesen

引用次数: 0

Endophilin-A/SH3GL2 calcium switch for synaptic autophagy induction is impaired by a Parkinson's risk variant. 帕金森氏症风险变体会损害突触自噬诱导的嗜内蛋白-A/SH3GL2钙离子开关。

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-04-17 DOI: 10.1080/15548627.2023.2200627

Marianna Decet, Sandra-Fausia Soukup

{"title":"Endophilin-A/SH3GL2 calcium switch for synaptic autophagy induction is impaired by a Parkinson's risk variant.","authors":"Marianna Decet, Sandra-Fausia Soukup","doi":"10.1080/15548627.2023.2200627","DOIUrl":"10.1080/15548627.2023.2200627","url":null,"abstract":"At the synapse, proteins are reused several times during neuronal activity, causing a decline in protein function over time. Although emerging evidence supports a role of autophagy in synaptic function, the precise molecular mechanisms linking neuronal activity, autophagy and synaptic dysfunction are vastly unknown. We show how extracellular calcium influx in the pre-synaptic terminal constitutes the initial stimulus for autophagosome formation in response to neuronal activity. This mechanism likely acts to rapidly support synaptic homeostasis and protein quality control when intense neuronal activity challenges the synaptic proteome. We identified a residue in the flexible region of EndoA (Endophilin A) that dictates calcium-dependent EndoA mobility from the plasma membrane to the cytosol, where this protein interacts with autophagic membranes to promote autophagosome formation. We discovered that a novel Parkinson's disease-risk mutation in SH3GL2 (SH3 domain containing GRB2 like 2, endophilin A1) disrupts the calcium sensing of SH3GL2, leading to an immobile protein that cannot respond to calcium influx and therefore disrupting autophagy induction at synapses. Our work shows how neuronal activity is connected with autophagy to maintain synaptic homeostasis and survival.","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"925-927"},"PeriodicalIF":14.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9303417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0