Autophagy最新文献

{"title":"The TBK1-SCF^FBXO3-TMEM192-TAX1BP1 axis: a novel regulatory mechanism for Lysophagy.","authors":"Na Yeon Park, Dong-Hyung Cho","doi":"10.1080/15548627.2025.2479669","DOIUrl":"https://doi.org/10.1080/15548627.2025.2479669","url":null,"abstract":"<p><p>Lysophagy, the selective macroautophagic/autophagic clearance of damaged lysosomes, is a critical mechanism for maintaining cellular homeostasis. Our recent study identified a novel regulatory axis involving TBK1, SCF^FBXO3, TMEM192, and TAX1BP1 that orchestrates lysophagic flux following lysosomal damage. We demonstrated that TBK1-dependent phosphorylation of FBXO3 facilitates its interaction with TMEM192, promoting its ubiquitination and subsequent recognition by the autophagy receptor TAX1BP1. Perturbing this pathway significantly reduces lysophagic flux and results in accumulation of damaged lysosomes. These findings establish a previously unrecognized mechanistic link between ubiquitination, receptor recruitment, and lysophagic degradation, broadening our understanding of lysosomal quality control.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATG2A acts as a tether to regulate autophagosome-lysosome fusion in neural cells.","authors":"Ze Zheng, Cuicui Ji, Hongyu Zhao, Yan G Zhao","doi":"10.1080/15548627.2025.2479427","DOIUrl":"https://doi.org/10.1080/15548627.2025.2479427","url":null,"abstract":"<p><p>The macroautophagy/autophagy proteins ATG2A and ATG2B transfer lipids for phagophore membrane growth. They also form stable complexes with WDR45 and WDR45B. Our previous study demonstrated that WDR45 and WDR45B mediate autophagosome-lysosome fusion in neural cells. Given the defective autophagosome formation in cells lacking both ATG2s, their role in later autophagy stages is hard to explore. Here, we report that in neuroblastoma-derived Neuro-2a (N2a) cells, knocking down (KD) <i>Atg2a</i>, but not <i>Atg2b</i>, results in significant accumulation of SQSTM1/p62 and MAP1LC3/LC3-II, indicating impaired autophagy. <i>Atg2a</i> deficiency does not affect autophagosome formation, but reduces colocalization of autophagosomal LC3 with late endosomal/lysosomal RFP-RAB7, suggesting impaired autophagosome-lysosome fusion. ATG2A interacts with the SNARE proteins STX17, SNAP29, and VAMP8, facilitating their assembly. Overexpression of ATG2A partially rescues the autophagosome-lysosome fusion defects in <i>Wdr45-</i> and <i>Wdr45b</i>-deficient cells. ATG2 and another tether protein, EPG5, function partially redundantly in mediating autophagosome-lysosome fusion. Thus, ATG2A plays a key role in neural autophagy by tethering autophagosomes with lysosomes for fusion.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cleavage of the selective autophagy receptor NBR1 by the PDCoV main protease NSP5 impairs autophagic degradation of the viral envelope protein.","authors":"Ke Li, Dong Chen, Kangli Zhao, Dan Liu, Dongni Kong, Yu Sun, Aohan Guan, Peng Zhou, Hui Jin, Anan Jongkaewwattana, Sizhu Suolang, Dang Wang, Hongbo Zhou, Rui Luo","doi":"10.1080/15548627.2025.2474576","DOIUrl":"10.1080/15548627.2025.2474576","url":null,"abstract":"<p><p>Porcine deltacoronavirus (PDCoV) is an emerging enteropathogenic coronavirus that causes severe diarrhea in neonatal piglets worldwide and presents a significant public health threat due to its potential for cross-species transmission. Selective macroautophagy/autophagy, mediated by autophagy receptors such as NBR1 (NBR1 autophagy cargo receptor), plays a key role in restricting viral infection and modulating the host immune response. In this study, we revealed that overexpression of NBR1 inhibits PDCoV replication, while its knockdown increases viral titers. Further analysis demonstrated that NBR1 interacts with the PDCoV envelope (E) protein independently of ubiquitination, directing it to phagophores for autophagic degradation to limit viral proliferation. To counteract this defense, PDCoV 3C-like protease, encoded by NSP5, cleaves porcine NBR1 at glutamine 353 (Q353), impairing its selective autophagy function and antiviral activity. Additionally, we demonstrated that NSP5 proteases from other coronaviruses including PEDV, TGEV, and SARS-CoV-2 also cleave NBR1 at the same site, suggesting that coronaviruses employ a conserved strategy of NSP5-mediated cleavage of NBR1 to evade host antiviral responses and facilitate infection. Overall, our study underscores the importance of NBR1-mediated selective autophagy in the host's defense against PDCoV and reveals a strategy by which PDCoV evades autophagic mechanisms to promote successful infection.<b>Abbreviation</b>: Cas9: CRISPR-associated protein 9; CC1: coiled-coil 1; Co-IP: co-immunoprecipitation; CRISPR: clustered regularly interspaced short palindromic repeats; GFP: green fluorescent protein; IFA: indirect immunofluorescence assay; KO: knockout; LIR: MAP1LC3/LC3-interacting region; mAb: monoclonal antibody; NBR1: NBR1 autophagy cargo receptor; NBR1-C: C-terminal fragment of NBR1; NBR1-N: N-terminal fragment of NBR1; OPTN: optineurin; pAb: polyclonal antibody; PB1: Phox/BEM1 domain; PDCoV: porcine deltacoronavirus; PEDV: porcine epidemic diarrhea virus; Q353A: a NBR1 construct with the glutamine (Q) residue at position 353 replaced with glutamic acid (A); SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; SQSTM1: sequestosome 1; TCID₅₀: 50% tissue culture infective dose; TGEV: porcine transmissible gastroenteritis virus; UBA: ubiquitin-associated domain; Ub: ubiquitin; WT: wild type; ZZ: ZZ-type zinc finger domain.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-16"},"PeriodicalIF":0.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"To degrade or not to degrade: how phase separation modulates selective autophagy.","authors":"Mariya Licheva, Riccardo Babic, Jeremy Pflaum, Hector Mancilla, Florian Wilfling, Claudine Kraft","doi":"10.1080/15548627.2025.2476025","DOIUrl":"10.1080/15548627.2025.2476025","url":null,"abstract":"<p><p>Selective macroautophagy/autophagy relies on newly formed double-membrane compartments, known as phagophores, to sequester and recycle diverse cellular components, including organelles, biomolecular condensates and protein aggregates, maturing into autophagosomes that fuse with the vacuole/lysosome. Autophagosomes originate at the cargo-vacuole/ER interface, where autophagy factors assemble into the phagophore assembly site (PAS). However, how autophagy proteins organize on the surface of structurally and biophysically different cargoes, and achieve spatial confinement at the PAS to support autophagosome formation remains unclear. Mechanisms governing cargo selection are also poorly understood. In this study, we demonstrate that receptor mobility, driven by low affinity cargo-receptor interactions, is crucial for rendering cellular structures degradable by autophagy. We show that cargo surface mobility, combined with the phase separation of scaffold proteins, drives the formation of early PAS precursors, termed \"initiation hubs\". These hubs dynamically rearrange at the cargo-vacuole/ER interface to promote autophagosome biogenesis, providing new insights into selective autophagy initiation.<b>Abbreviation:</b> Ape1: aminopeptidase I; Atg: autophagy related; Cvt pathway: cytoplasm-to-vacuole targeting pathway; GBP-GFP: GFP binding protein-Green Fluorescent Protein; ENDs: Ede1-dependent endocytic protein deposits; ER: endoplasmic reticulum; PAS: phagophore-assembly site; RB1CC1/FIP200: RB1-inducible coiled-coil 1; SQSTM1/p62: sequestosome 1; ULK1: unc-51 like kinase 1.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LAMP2-FLOT2 interaction enhances autophagosome-lysosome fusion to protect the septic heart in response to ILC2.","authors":"Rongjiao Shao, Weizhuo Liu, Yuxiao Feng, Xiaoyu Guo, Zhenyu Ren, Xumin Hou, Bin He","doi":"10.1080/15548627.2025.2469207","DOIUrl":"https://doi.org/10.1080/15548627.2025.2469207","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Cardiac dysfunction is a serious complication of sepsis-induced multiorgan failure in intensive care units and is characterized by an uncontrolled immune response to overwhelming infection. Type 2 innate lymphoid cells (ILC2s), as a part of the innate immune system, play a crucial role in the inflammatory process of heterogeneous cardiac disorders. However, the role of ILC2 in regulating sepsis-induced cardiac dysfunction and its underlying mechanism remain unknown. The present study demonstrated that autophagic flux blockage exacerbated inflammatory response and cardiac dysfunction, which was associated with mortality of sepsis. Using a cecal ligation and puncture (CLP) mouse sepsis model, we observed an expansion of ILC2s in the septic heart. Furthermore, IL4 derived from ILC2 mitigated cardiac inflammatory responses and improved cardiac function during sepsis. Additionally, IL4 enhanced LAMP2 (lysosomal associated membrane protein 2) expression through STAT3 (signal transducer and activator of transcription 3) activation to stabilize lysosomal homeostasis and rescue the impaired autophagic flux during sepsis. Notably, LAMP2 was preferentially bound to FLOT2 (flotillin 2) after IL4 exposure, and the interaction enhanced autophagosome-lysosome fusion in cardiac endothelial cells. Loss of FLOT2 reversed the regulatory effects of LAMP2 on autophagy mediated by IL4, leading to autophagosome accumulation and suppressed autophagosome clearance. Conclusively, these findings provide novel insights that ILC2 regulates incomplete autophagic flux to protect septic heart and expand our understanding of immunoregulation for sepsis.&lt;b&gt;Abbreviation&lt;/b&gt;: ACTB: actin beta; ACTN: actinin, alpha; ADGRE1/F4/80: adhesion G protein-coupled receptor E1; ANXA5/annexin V: annexin A5; AO: acridine orange; BECN1/Beclin1: beclin 1, autophagy related; CKM: creatine kinase, muscle; CKB: creatine kinase, brain; CLP: cecal ligation and puncture; CO: cardiac output; CQ: chloroquine; CTS: cathepsin; DAPI: 4'6-diamidino-2-phenylindole; EC: endothelial cell; EF: ejection fraction; ELISA: enzyme-linked immunosorbent assay; FLOT: flotillin; FS: fractional shortening; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GATA3: GATA binding protein 3; GLB1/β-Gal: galactosidase, beta 1; HCMEC: human cardiac microvascular endothelial cell; IL: interleukin; ILC: innate lymphoid cell; IL1RL1/ST2: interleukin 1 receptor-like 1; IL4c: IL4 complex; IL7R/CD127: interleukin 7 receptor; KEGG: Kyoto Encyclopedia of Genes and Genomes; LAMP: lysosomal-associated membrane protein; LDH: lactate dehydrogenase; LMP: lysosome membrane permeabilization; LPS: lipopolysaccharide; LVEDd: left ventricular end-diastole diameter; LVEDV: left ventricular end-diastole volume; LVESd: left ventricular end-systolic diameter; LVESV: left ventricular end-systole volume; MAN: mannosidase alpha; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MS: mass spectrometry; PECAM1/CD31: platelet/endothelial cel","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-23"},"PeriodicalIF":0.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-associated mutations in autophagy-related proteins analyzed in yeast and human cells.","authors":"Yuchen Lei, Louise Uoselis, Dimitra Dialynaki, Ying Yang, Michael Lazarou, Daniel J Klionsky","doi":"10.1080/15548627.2025.2471142","DOIUrl":"10.1080/15548627.2025.2471142","url":null,"abstract":"<p><p>Macroautophagy/autophagy is a conserved process among eukaryotes and is essential to maintain cell homeostasis; the dysregulation of autophagy has been linked with multiple human diseases, including cancer. However, not many studies have focused on the cancer-related mutations in ATG (autophagy related) proteins, which are likely to affect the protein function, influence autophagy activity and further contribute to the progression of the disease. In this study, we focused on the four ATG4 isoforms, which have a higher mutation frequency compared with the other core ATG proteins (i.e. those involved in autophagosome formation). We first studied the mutations in conserved residues and characterized one cancer-associated mutation that significantly impairs protein function and autophagy activity. Extending the study, we determined a region around the mutant residue to be essential for protein function, which had yet to be examined in previous studies. In addition, we created a yeast system expressing the human ATG4B protein to study mutations in the residues that are not conserved from human to yeast. Using this yeast model, we identified six cancer-associated mutations affecting autophagy. The effects of these mutations were further tested in mammalian cells using a quadruple <i>ATG4</i> gene knockout cell line. Our study proves the principle of using human disease-associated mutations to study Atg proteins in yeast and generates a yeast tool that is helpful for a rapid screen of mutations to determine the autophagy phenotype, providing a new perspective in studying autophagy and its relation with cancer.<b>Abbreviations:</b> 4KO: <i>ATG4</i> tetra knockout; ATG: autophagy related; BafA1: bafilomycin A₁; GFP: green fluorescent protein; LC3-II: PE-conjugated form of LC3B; ORF: open reading frame; PE: phosphatidylethanolamine; RFP: red fluorescent protein; SEP: superecliptic pHluorin; Ubl: ubiquitin-like; UCEC: uterine corpus endometrial carcinoma.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-17"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy induced by mechanical stress sensitizes cells to ferroptosis by NCOA4-FTH1 axis.","authors":"Chenyu Luo, Haisheng Liang, Mintao Ji, Caiyong Ye, Yiping Lin, Yuhan Guo, Zhisen Zhang, Yinyin Shu, Xiaoni Jin, Shuangshuang Lu, Wanling Lu, Yazheng Dang, Hong Zhang, Bingyan Li, Guangming Zhou, Zengli Zhang, Lei Chang","doi":"10.1080/15548627.2025.2469129","DOIUrl":"10.1080/15548627.2025.2469129","url":null,"abstract":"<p><p>Ferroptosis is an iron-dependent regulated form of cell death implicated in various diseases, including cancers, with its progression influenced by iron-dependent peroxidation of phospholipids and dysregulation of the redox system. Whereas the extracellular matrix of tumors provides mechanical cues influencing tumor initiation and progression, its impact on ferroptosis and its mechanisms remains largely unexplored. In this study, we reveal that heightened mechanical tension sensitizes cells to ferroptosis, whereas decreased mechanics confers resistance. Mechanistically, reduced mechanical tension reduces intracellular free iron levels by enhancing FTH1 protein expression. Additionally, low mechanics significantly diminishes NCOA4, pivotal in mediating FTH1 phase separation-induced ferritinophagy. Targeting NCOA4 effectively rescues ferroptosis susceptibility under low mechanical tension through modulation of FTH1 phase separation-driven autophagy. In conclusion, our findings demonstrate that mechanics regulates iron metabolism via NCOA4-FTH1 phase separation-mediated autophagy, thereby influencing ferroptosis sensitivity and offering promising therapeutic avenues for future exploration.<b>Abbreviations:</b> ACO1: aconitase 1; ATG5: autophagy related 5; DMSO: dimethyl sulfoxide; EGFP: enhanced green fluorescent protein; FACS: fluorescence-activated cell sorting; FER-1: ferrostatin-1; FTH1: ferritin heavy chain 1; FTL: ferritin light chain; GPX4: glutathione peroxidase 4; IR: ionizing radiation; IREB2: iron responsive element binding protein 2; NCOA4: nuclear receptor coactivator 4; NFE2L2: NFE2 like bZIP transcription factor 2; NOPP: norepinephrine; PBS: phosphate-buffered saline; PI: propidium iodide; RSL3: (1S,3 R)-RSL3; TCGA: The Cancer Genome Atlas; WWTR1: WW domain containing transcription regulator 1; YAP1: Yes1 associated transcriptional regulator.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-20"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leucine accelerates atherosclerosis through dose-dependent MTOR activation in macrophages.","authors":"Xiangyu Zhang, Ali Ajam, Ziyang Liu, Doureradjou Peroumal, Saifur R Khan, Babak Razani","doi":"10.1080/15548627.2025.2474603","DOIUrl":"10.1080/15548627.2025.2474603","url":null,"abstract":"<p><p>The role of diet in driving cardiovascular disease (CVD) is well-recognized, particularly in the case of lipids. Dietary protein on the other hand has been heralded as an overall metabolically beneficial nutrient with popularity in the fitness community and in weight-loss regimens. Pursuant to epidemiological studies raising a CVD risk signal for excessive protein intake, we initially conducted murine studies establishing an atherogenic role for dietary protein, the critical involvement of macrophage MTORC1 signaling, and downstream inhibition of protective macroautophagy/autophagy pathways. In recent work, we confirm these findings in monocytes from humans consuming protein and dissect the MTORC1-autophagy cascade in human macrophages. We also identify leucine as the single most important amino acid, observing dose-dependent activation of MTOR whereby only leucine concentrations above a threshold trigger pathogenic signaling and monocyte/macrophage dysfunction. Using mouse models fed diets with modulated protein and leucine content, we confirm this threshold effect in driving atherosclerosis. Our findings establish a pathogenic role for dietary leucine in CVD and raise the promise of therapeutic strategies aimed at selective inhibition of macrophage leucine-MTOR signaling.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mitophagy receptor BNIP3L/Nix coordinates nuclear calcium signaling to modulate the muscle phenotype.","authors":"Jared T Field, Donald Chapman, Yan Hai, Saeid Ghavami, Adrian R West, Berkay Ozerklig, Ayesha Saleem, Julia Kline, Asher A Mendelson, Jason Kindrachuk, Barbara Triggs-Raine, Joseph W Gordon","doi":"10.1080/15548627.2025.2476872","DOIUrl":"https://doi.org/10.1080/15548627.2025.2476872","url":null,"abstract":"<p><p>Mitochondrial quality control is critical in muscle to ensure contractile and metabolic function. BNIP3L/Nix is a BCL2 member, a mitophagy receptor, and has been implicated in muscle atrophy. Human genome-wide association studies (GWAS) suggest altered BNIP3L expression could predispose to mitochondrial disease. To investigate BNIP3L function, we generated a muscle-specific knockout model. <i>bnip3l</i> knockout mice displayed a ragged-red fiber phenotype, along with accumulation of mitochondria and endo/sarcoplasmic reticulum with altered morphology. Intriguingly, <i>bnip3l</i> knockout mice were more insulin sensitive with a corresponding increase in glycogen-rich muscle fibers. Kinome and gene expression analyses revealed that <i>bnip3l</i> knockout impairs NFAT and MSTN (myostatin) signaling, with alterations in muscle fiber-type and evidence of regeneration. Mechanistic experiments demonstrated that BNIP3L modulates mitophagy, along with reticulophagy leading to altered nuclear calcium signaling. Collectively, these observations identify novel roles for BNIP3L coordinating selective autophagy, oxidative gene expression, and signaling pathways that maintain the muscle phenotype.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A distinctive form of autophagy induced by oncogenic RAS.","authors":"Xiaojuan Wang, Shulin Li, Min Zhang, Liang Ge","doi":"10.1080/15548627.2025.2468917","DOIUrl":"10.1080/15548627.2025.2468917","url":null,"abstract":"<p><p>RAS mutations enhance macroautophagy/autophagy in tumor cells, crucial for their growth and survival, making autophagy a promising therapeutic target for RAS-mutant cancers. However, the distinction between RAS-induced autophagy and physiological autophagy is not well understood. We recently identified a unique form of autophagy, RAS-induced non-canonical autophagy via ATG8ylation (RINCAA), which differs from starvation-induced autophagy. RINCAA is regulated by different sets of autophagic factors and forms structures distinct from the double-membrane autophagosome known as RAS-induced multivesicular/multilaminar bodies of ATG8ylation (RIMMBA). A key feature of RINCAA is the phosphorylation of PI4KB by ULK1, and inhibiting this phosphorylation shows superior effects compared to general autophagy inhibitors. This work suggests a potential for specifically targeting autophagy in RAS-driven cancers as a therapeutic strategy.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}