Autophagy最新文献

{"title":"DIRAS3 induces autophagy and enhances sensitivity to anti-autophagic therapy in KRAS-driven pancreatic and ovarian carcinomas","authors":"Gamze Bildik, Joshua P. Gray, Weiqun Mao, Hailing Yang, Rumeysa Ozyurt, Vivian R. Orellana, Olivier De Wever, Mark S. Carey, Robert C. Bast, Zhen Lu","doi":"10.1080/15548627.2023.2299516","DOIUrl":"https://doi.org/10.1080/15548627.2023.2299516","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) and low-grade ovarian cancer (LGSOC) are characterized by the prevalence of KRAS oncogene mutations. DIRAS3 is the first endogenous non-RAS protein that hete...","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":"27 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139083154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disrupted endoplasmic reticulum-mediated autophagosomal biogenesis in a <i>Drosophila</i> model of C9-ALS-FTD.","authors":"Hyun Sung, Thomas E Lloyd","doi":"10.1080/15548627.2023.2249750","DOIUrl":"10.1080/15548627.2023.2249750","url":null,"abstract":"<p><strong>Abbreviations: </strong>3R: UAS construct expressing 3 G₄C₂ repeats (used as control); 3WJ: three-way junction; 12R: UAS construct expressing leader sequence and 12 G₄C₂ repeats; 30R: UAS construct expressing 30 G₄C₂ repeats; 36R: UAS construct expressing 36 G₄C₂ repeats; 44R: UAS construct expressing leader sequence and 44 G₄C₂ repeats; ALS: amyotrophic lateral sclerosis; Atg: autophagy related; atl: atlastin; C9-ALS-FTD: ALS or FTD caused by hexanuleotide repeat expansion in <i>C9orf72</i>; ER: endoplasmic reticulum; FTD: frontotemporal dementia; HRE: GGGGCC hexanucleotide repeat expansion; HSP: hereditary spastic paraplegia; Lamp1: lysosomal associated membrane protein 1; MT: microtubule; NMJ: neuromuscular junction; Rab: Ras-associated binding GTPase; RAN: repeat associated non-AUG (RAN) translation; RO-36: UAS construct expression \"RNA-only\" version of 36 G₄C₂ repeats in which stop codons in all six reading frames are inserted.; Rtnl1: Reticulon-like 1; SN: segmental nerve; TFEB/Mitf: transcription factor EB/microphthalmia associated transcription factor (<i>Drosophila</i> ortholog of TFEB); TrpA1: transient receptor potential cation channel A1; VAPB: VAMP associated protein B and C; VNC: ventral nerve cord (spinal cord in <i>Drosophila</i> larvae).</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"94-113"},"PeriodicalIF":14.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10168582","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}

{"title":"Atl (atlastin) regulates mTor signaling and autophagy in Drosophila muscle through alteration of the lysosomal network.","authors":"Saurabh Srivastav, Kevin van der Graaf, Pratibha Singh, Alloysius Budi Utama, Matthew D Meyer, James A McNew, Michael Stern","doi":"10.1080/15548627.2023.2249794","DOIUrl":"10.1080/15548627.2023.2249794","url":null,"abstract":"<p><strong>Abbreviations: </strong>atl atlastin; ALR autophagic lysosome reformation; ER endoplasmic reticulum; GFP green fluorescent protein; HSP hereditary spastic paraplegia; Lamp1 lysosomal associated membrane protein 1 PolyUB polyubiquitin; RFP red fluorescent protein; spin spinster; mTor mechanistic Target of rapamycin; VCP valosin containing protein.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"131-150"},"PeriodicalIF":14.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10177467","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}

{"title":"The presence of blastocyst within the uteri facilitates lumenal epithelium transformation for implantation via upregulating lysosome proteostasis activity.","authors":"Peike Wang, Shuailin Du, Chuanhui Guo, Zhangli Ni, Ziying Huang, Na Deng, Haili Bao, Wenbo Deng, Jinhua Lu, Shuangbo Kong, Hua Zhang, Haibin Wang","doi":"10.1080/15548627.2023.2247747","DOIUrl":"10.1080/15548627.2023.2247747","url":null,"abstract":"<p><strong>Abbreviations: </strong>ACTB: actin beta; AREG: amphiregulin; ATP6V0A4: ATPase, H⁺ transporting, lysosomal V0 subunit A4; Baf A1: bafilomycin A₁; BSA: bovine serum albumin; CLDN1: claudin 1; CTSB: cathepsin B; DEGs: differentially expressed genes; E₂: 17β-estradiol; ESR: estrogen receptor; GATA2: GATA binding protein 2; GLA: galactosidase, alpha; GO: gene ontology; HBEGF: heparin-binding EGF-like growth factor; IGF1R: insulin-like growth factor 1 receptor; Ihh: Indian hedgehog; ISH: in situ hybridization; LAMP1: lysosomal-associated membrane protein 1; LCM: laser capture microdissection; Le: lumenal epithelium; LGMN: legumain; LIF: leukemia inhibitory factor; LIFR: LIF receptor alpha; MSX1: msh homeobox 1; MUC1: mucin 1, transmembrane; P₄: progesterone; PBS: phosphate-buffered saline; PCA: principal component analysis; PPT1: palmitoyl-protein thioesterase 1; PGR: progesterone receptor; PSP: pseudopregnancy; PTGS2/COX2: prostaglandin-endoperoxide synthase 2; qPCR: quantitative real-time polymerase chain reaction; SP: pregnancy; TFEB: transcription factor EB.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"58-75"},"PeriodicalIF":14.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10302103","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}

{"title":"ATPase-regulated autophagosome biogenesis.","authors":"Viola Nähse, Kay O Schink, Harald Stenmark","doi":"10.1080/15548627.2023.2255967","DOIUrl":"10.1080/15548627.2023.2255967","url":null,"abstract":"<p><p>Omega-shaped domains of the endoplasmic reticulum, known as omegasomes, have been suggested to contribute to autophagosome biogenesis, although their exact function is not known. Omegasomes are characterized by the presence of the double FYVE domain containing protein ZFYVE1/DFCP1, but it has remained a paradox that depletion of ZFYVE1 does not prevent bulk macroautophagy/autophagy. We recently showed that ZFYVE1 contains an N-terminal ATPase domain which dimerizes upon ATP binding. Mutations in the ATPase domain that inhibit ATP binding or hydrolysis do not prevent omegasome expansion and maturation. However, omegasome constriction is inhibited by these mutations, which results in an increased lifetime and thereby higher number of omegasomes. Interestingly, whereas <i>ZFYVE1</i> knockout or mutations do not significantly affect bulk autophagy, selective autophagy of mitochondria, protein aggregates and micronuclei is inhibited. We propose that ATP binding and hydrolysis control the di- or multimerization state of ZFYVE1 which could provide the mechanochemical energy to drive large omegasome constriction and autophagosome completion.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"218-219"},"PeriodicalIF":13.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10361527","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}

{"title":"Pristimerin suppresses AIM2 inflammasome by modulating AIM2-PYCARD/ASC stability via selective autophagy to alleviate tendinopathy.","authors":"Huaji Jiang, Yingchao Xie, Jiansen Lu, Hongyu Li, Ke Zeng, Zhiqiang Hu, Dan Wu, Jianwu Yang, Zhenxia Yao, Huadan Chen, Xiaoqian Gong, Xiao Yu","doi":"10.1080/15548627.2023.2249392","DOIUrl":"10.1080/15548627.2023.2249392","url":null,"abstract":"<p><p>Macroautophagy/autophagy plays an important role in regulating cellular homeostasis and influences the pathogenesis of degenerative diseases. Tendinopathy is characterized by tendon degeneration and inflammation. However, little is known about the role of selective autophagy in tendinopathy. Here, we find that pristimerin (PM), a quinone methide triterpenoid, is more effective in treating tendinopathy than the first-line drug indomethacin. PM inhibits the AIM2 inflammasome and alleviates inflammation during tendinopathy by promoting the autophagic degradation of AIM2 through a PYCARD/ASC-dependent manner. A mechanistic study shows that PM enhances the K63-linked ubiquitin chains of PYCARD/ASC at K158/161, which serves as a recognition signal for SQSTM1/p62-mediated autophagic degradation of the AIM2-PYCARD/ASC complex. We further identify that PM binds the Cys53 site of deubiquitinase USP50 through the Michael-acceptor and blocks the binding of USP50 to PYCARD/ASC, thereby reducing USP50-mediated cleavage of K63-linked ubiquitin chains of PYCARD/ASC. Finally, PM treatment <i>in vivo</i> generates an effect comparable to inflammasome deficiency in alleviating tendinopathy. Taken together, these findings demonstrate that PM alleviates the progression of tendinopathy by modulating AIM2-PYCARD/ASC stability <i>via</i> SQSTM1/p62-mediated selective autophagic degradation, thus providing a promising autophagy-based therapeutic for tendinopathy.<b>Abbreviations:</b> 3-MA: 3-methyladenine; AIM2: absent in melanoma 2; AT: Achilles tenotomy; ATP: adenosine triphosphate; BMDMs: bone marrow-derived macrophages; CHX: cycloheximide; <i>Col3a1</i>: collagen, type III, alpha 1; CQ: chloroquine; Cys: cysteine; DARTS: drug affinity responsive target stability; DTT: dithiothreitol; DUB: deubiquitinase; gDNA: genomic DNA; GSH: glutathione; His: histidine; IL1B/IL-1β: interleukin 1 beta; IND: indomethacin; IP: immunoprecipitation; LPS: lipopolysaccharide; MMP: mitochondrial membrane potential; NLRP3: NLR family, pyrin domain containing 3; PM: pristimerin; PYCARD/ASC: PYD and CARD domain containing; SN: supernatants; SOX9: SRY (sex determining region Y)-box 9; SQSTM1: sequestosome 1; <i>Tgfb</i>: transforming growth factor, beta; TIMP3: tissue inhibitor of metalloproteinase 3; TNMD: tenomodulin; TRAF6: TNF receptor-associated factor 6; Ub: ubiquitin; USP50: ubiquitin specific peptidase 50; WCL: whole cell lysates.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"76-93"},"PeriodicalIF":14.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10121577","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}

{"title":"Interplay of energy metabolism and autophagy.","authors":"Yuyao Feng, Ying Chen, Xiaoyong Wu, Junye Chen, Qingyan Zhou, Bao Liu, Liqin Zhang, Cong Yi","doi":"10.1080/15548627.2023.2247300","DOIUrl":"10.1080/15548627.2023.2247300","url":null,"abstract":"<p><p>Macroautophagy/autophagy, is widely recognized for its crucial role in enabling cell survival and maintaining cellular energy homeostasis during starvation or energy stress. Its regulation is intricately linked to cellular energy status. In this review, covering yeast, mammals, and plants, we aim to provide a comprehensive overview of the understanding of the roles and mechanisms of carbon- or glucose-deprivation related autophagy, showing how cells effectively respond to such challenges for survival. Further investigation is needed to determine the specific degraded substrates by autophagy during glucose or energy deprivation and the diverse roles and mechanisms during varying durations of energy starvation.<b>Abbreviations:</b> ADP: adenosine diphosphate; AMP: adenosine monophosphate; AMPK: AMP-activated protein kinase; ATG: autophagy related; ATP: adenosine triphosphate; ER: endoplasmic reticulum; ESCRT: endosomal sorting complex required for transport; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GD: glucose deprivation; GFP: green fluorescent protein; GTPases: guanosine triphosphatases; HK2: hexokinase 2; <i>K phaffii</i>: <i>Komagataella phaffii</i>; LD: lipid droplet; MAP1LC3/LC3: microtubule-associated protein1 light chain 3; MAPK: mitogen-activated protein kinase; Mec1: mitosis entry checkpoint 1; MTOR: mechanistic target of rapamycin kinase; NAD (+): nicotinamide adenine dinucleotide; OGD: oxygen and glucose deprivation; PAS: phagophore assembly site; PCD: programmed cell death; PtdIns3K: class III phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; ROS: reactive oxygen species; <i>S. cerevisiae</i>: <i>Saccharomyces cerevisiae</i>; SIRT1: sirtuin 1; Snf1: sucrose non-fermenting 1; STK11/LKB1: serine/threonine kinase 11; TFEB: transcription factor EB; TORC1: target of rapamycin complex 1; ULK1: unc-51 like kinase 1; Vps27: vacuolar protein sorting 27; Vps4: vacuolar protein sorting 4.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"4-14"},"PeriodicalIF":14.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10151035","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}

{"title":"Melatonin attenuates sepsis-induced acute kidney injury by promoting mitophagy through SIRT3-mediated TFAM deacetylation.","authors":"Zhiya Deng, Man He, Hongbin Hu, Wenqian Zhang, Yaoyuan Zhang, Yue Ge, Tongtong Ma, Jie Wu, Lulan Li, Maomao Sun, Sheng An, Jiaxin Li, Qiaobing Huang, Shenhai Gong, Jiaxing Zhang, Zhongqing Chen, Zhenhua Zeng","doi":"10.1080/15548627.2023.2252265","DOIUrl":"10.1080/15548627.2023.2252265","url":null,"abstract":"<p><strong>Abbreviations: </strong>AKI: acute kidney injury; ATP: adenosine triphosphate; BUN: blood urea nitrogen; CLP: cecal ligation and puncture; eGFR: estimated glomerular filtration rate; H&E: hematoxylin and eosin staining; LCN2/NGAL: lipocalin 2; LPS: lipopolysaccharide; LTL: lotus tetragonolobus lectin; mKeima: mitochondria-targeted Keima; mtDNA: mitochondrial DNA; PAS: periodic acid - Schiff staining; RTECs: renal tubular epithelial cells; SAKI: sepsis-induced acute kidney injury; Scr: serum creatinine; SIRT3: sirtuin 3; TFAM: transcription factor A, mitochondrial; TMRE: tetramethylrhodamine.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"151-165"},"PeriodicalIF":13.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10131476","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}

{"title":"A new regulator of autophagy initiation in glia.","authors":"Linfang Wang, Shiping Zhang, Shuanglong Yi, Margaret S Ho","doi":"10.1080/15548627.2023.2251821","DOIUrl":"10.1080/15548627.2023.2251821","url":null,"abstract":"<p><p>Macroautophagy/autophagy is the major degradation pathway in neurons for eliminating damaged proteins and organelles in Parkinson disease (PD). Like neurons, glial cells are important contributors to PD, yet how autophagy is executed in glia and whether it is using similar interplay as in neurons or other tissues, remain largely elusive. Recently, we reported that the PD risk factor, GAK/aux (cyclin-G-associated kinase/auxilin), regulates the onset of glial autophagy. In the absence of GAK/aux, the number and size of the autophagosomes and autophagosomal precursors increase in adult fly glia and mouse microglia. The protein levels of components in the initiation and class III phosphatidylinositol 3-kinase (PtdIns3K) complexes are generally upregulated. GAK/aux interacts with the master initiation regulator ULK1/Atg1 (unc-51 like autophagy activating kinase 1) via its uncoating domain, hinders autophagy activation by competing with ATG13 (autophagy related 13) for binding to the ULK1 C terminus, and regulates ULK1 trafficking to phagophores. Nonetheless, lack of GAK/aux impairs the autophagic flux and blocks substrate degradation, suggesting that GAK/aux might play additional roles. Overall, our findings reveal a new regulator of autophagy initiation in glia, advancing our understanding on how glia contribute to PD in terms of eliminating pathological protein aggregates.<b>Abbreviations:</b> ATG13: autophagy related 13; GAK/aux: cyclin G associated kinase/auxilin; PtdIns3K: phosphatidylinositol 3-kinase; PD: Parkinson disease; ULK1/Atg1: unc-51 like autophagy activating kinase 1.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"207-209"},"PeriodicalIF":14.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10095108","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}

{"title":"ATG3 proteins possess a unique amphipathic α-helix essential for the Atg8/LC3 lipidation reaction.","authors":"Taki Nishimura, Gianmarco Lazzeri, Sharon A Tooze, Roberto Covino","doi":"10.1080/15548627.2023.2255458","DOIUrl":"10.1080/15548627.2023.2255458","url":null,"abstract":"<p><p>In our recent paper, we uncovered that ATG3 exhibits a large degree of structural dynamics on autophagic membranes to efficiently carry out LC3 lipidation. ATG3 proteins possess an amphipathic α-helix (AH) identified by a small number of bulky and hydrophobic residues. This biophysical fingerprint allows for transient membrane association of ATG3 and facilitates its enzymatic reaction. This study will pave the way for a structural and mechanistic understanding of how membrane association of ATG proteins is orchestrated during autophagosome formation.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"212-213"},"PeriodicalIF":14.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10173349","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}