Autophagy最新文献

{"title":"Unconventional role of ATG16L1 in the control of ATP compartmentalization during apoptosis.","authors":"Elena Terraza-Silvestre, Julia Bandera-Linero, Daniel Oña-Sánchez, Felipe X Pimentel-Muiños","doi":"10.1080/15548627.2025.2519051","DOIUrl":"10.1080/15548627.2025.2519051","url":null,"abstract":"<p><p>The autophagy mediator ATG16L1 forms part of a complex that is essential for MAP1LC3/LC3 lipidation and autophagosome formation in the canonical macroautophagic/autophagic pathway. However, ATG16L1 is also involved in unconventional activities where LC3 becomes lipidated in single-membrane structures unrelated to double-membrane autophagosomes. Such atypical activities usually require the C-terminal domain of the molecule that includes 7 WD40-type repetitions (WD40 domain, WDD). The WDD acts as a docking site for upstream inducers that engage the LC3 lipidation ability of ATG16L1 in alternative membrane compartments. Given that this domain is absent in the yeast Atg16 ortholog, an intriguing idea proposes that it was added to the primitive protein during evolution to perform new physiological roles required by the appearance of multicellularity. Identification of such atypical activities and their physiological implications at the organismal level are important issues that remain to be clarified. In a recent report we describe an unconventional autophagic pathway that restrains the immunogenic potential of apoptosis, a key feature of homeostatic and developmentally regulated cell death in multicellular organisms. This signaling route emanates from apoptotic mitochondria and induces the formation of single-membrane, LC3-positive vesicles through a mechanism that requires the WDD of ATG16L1. The induced vesicles sequester ATP to inhibit the amount of ATP released from apoptotic cells and, consequently, prevent the activation of co-cultured phagocytes. Thus, this is a pathway that contributes to maintain the immunosilent nature of apoptotic cell death.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"2085-2087"},"PeriodicalIF":14.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287524","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}

{"title":"ATG16L1 WD domain and linker regulates lipid trafficking to maintain plasma membrane integrity to limit influenza virus infection.","authors":"Benjamin Bone, Luke Griffith, Matthew Jefferson, Yohei Yamauchi, Thomas Wileman, Penny P Powell","doi":"10.1080/15548627.2025.2482516","DOIUrl":"10.1080/15548627.2025.2482516","url":null,"abstract":"<p><p>The non-canonical functions of autophagy protein ATG16L1 are dependent on a C-terminal WD domain. Recent studies show that the WD domain is required for conjugation of LC3 to single membranes during endocytosis and phagocytosis, where it is thought to promote fusion with lysosomes. Studies in cells lacking the WD domain suggest additional roles in the regulation of cytokine receptor recycling and plasma membrane repair. The WD domain also protects mice against lethal influenza virus <i>in vivo</i>. Here, analysis of mice lacking the WD domain (ΔWD) shows enrichment of cholesterol in brain tissue suggesting a role for the WD domain in cholesterol transport. Brain tissue and cells from ΔWD mice showed reduced cholesterol and phosphatidylserine (PS) in the plasma membrane. Cells from ΔWD mice also showed an intracellular accumulation of cholesterol predominantly in late endosomes. Infection studies using IAV suggest that the loss of cholesterol and PS from the plasma membrane in cells from ΔWD mice results in increased endocytosis and nuclear delivery of IAV, as well as increased <i>Ifnb</i>/<i>Ifnβ</i> and <i>Isg15</i> gene expression. Upregulation of <i>Il6</i>, <i>Ifnb</i> and <i>Isg15</i> mRNA were observed in \"ex vivo\" precision cut lung slices from ΔWD mice both at rest and in response to IAV infection. Overall, we present evidence that regulation of lipid transport by the WD domain of ATG16L1 may have downstream implications in attenuating viral infection and limiting lethal cytokine signaling.<b>Abbreviations</b>: BMDM: bone marrow-derived macrophages, CASM: conjugation of ATG8 to single membranes, CCD: coil-coil domain, IAV: influenza virus A, IFIT1: interferon-induced protein with tetratricopeptide repeats 1, IFITM3: interferon induced transmembrane protein 3, IFN: interferon, ISG15: ISG15 ubiquitin-like modifier, LANDO: LC3-associated endocytosis, LAP: LC3-associated phagocytosis, LDL: low density lipoprotein, NP: nucleoprotein, PS: phosphatidylserine, WD: WD40-repeat-containing C-terminal domain, WT: wild type.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1911-1926"},"PeriodicalIF":14.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722982","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}

{"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":"10.1080/15548627.2025.2469207","url":null,"abstract":"<p><p>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.<b>Abbreviation</b>: 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":"1888-1910"},"PeriodicalIF":14.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598496","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}

{"title":"RHOD mediates ATG9A trafficking to promote autophagosome formation during autophagy in cancer.","authors":"Sijia Wang, Jing Ren, Jinghan Chi, Yifei Guan, Ran Zheng, Juan Wang, Xinhui Liu, Hua Huang","doi":"10.1080/15548627.2025.2484604","DOIUrl":"10.1080/15548627.2025.2484604","url":null,"abstract":"<p><p>ATG9A is a transmembrane protein essential for macroautophagy/autophagy that drives autophagosome formation by delivering essential proteins and lipids to the phagophore through vesicle trafficking. Here, we demonstrate that the atypical Rho GTPase RHOD is required for ATG9A trafficking and stimulates autophagosome formation. Upon starvation, RHOD interacted with ATG9A and accompanied ATG9A trafficking from the Golgi toward phagophores. In addition, starvation-induced high levels of RHOD resulted in Golgi fragmentation to further promote ATG9A vesicle export from the trans-Golgi network to the peripheral region. Loss of RHOD suppressed ATG9A trafficking and reduced the distribution of ATG9A on the phagophore. Moreover, WHAMM (WASP homolog associated with actin, golgi membranes and microtubules) forms a complex with RHOD and participates in this process in a RHOD-dependent manner. Importantly, RHOD mutants, which lack the exon II-containing effector region motif that is required for ATG9A binding or lack the CAAX box that is responsible for membrane targeting, fail to stimulate ATG9A trafficking and autophagosome formation. Furthermore, RHOD plays a distinct suppressor role in tumor development, partly associated with its regulatory effect on autophagy. These findings reveal the important roles of RHOD in autophagy and tumor development.<b>Abbreviation</b>: ATG9A: autophagy related 9A; BafA1: bafilomycin A₁; BiFC: bimolecular fluorescence complementation; co-IP: co-immunoprecipitation; EBSS: Earle's balanced salt solution; FM: full culture medium; KO: knockout; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; PUP-IT: pupylation-based interaction tagging; RHOD: ras homolog family member D; SQSTM1: sequestosome 1; TGN: trans-Golgi network; VC: Venus C-terminal; VN: Venus N-terminal; WHAMM: WASP homolog associated with actin, golgi membranes and microtubules; WIPI2: WD repeat domain, phosphoinositide interacting 2; WT: wild-type; 3-MA: phosphatidylinositol 3-kinase (PtdIns3K) inhibitor 3-methyladenine.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1976-1994"},"PeriodicalIF":14.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722986","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}

{"title":"PRMT1 (protein arginine methyltransferase 1) is essential for neuromuscular junction and mitochondrial homeostasis via mitophagy regulation.","authors":"Ju-Hyeon Bae, Chang-Lim You, Yideul Jeong, June Kim, Jinwoo Lee, Hyeon-Ju Jeong, Hyebeen Kim, Tuan Anh Vuong, Youngdae Gwon, Gyu-Un Bae, Jong-Sun Kang","doi":"10.1080/15548627.2025.2551477","DOIUrl":"https://doi.org/10.1080/15548627.2025.2551477","url":null,"abstract":"<p><p>The neuromuscular junction (NMJ) is essential for transmitting neural stimulus to muscles, triggering muscle contraction. Mitochondria are enriched in NMJ to support the energy needs required for neuromuscular function and stability. Thus, maintaining mitochondrial homeostasis through the clearance of damaged mitochondria, a process known as mitophagy, is vital for preserving neuromuscular health. Here, we highlight the crucial role of muscle PRMT1 in maintaining NMJ and mitochondrial homeostasis via mitophagy regulation. PRMT1 is distinctively expressed in myofibers, accumulating in the postsynaptic area, with its levels upregulated in denervated muscles. PRMT1-ablated muscles displayed disrupted NMJs and an accumulation of abnormal mitochondria, accompanied by increased mitochondrial oxidative stress. Additionally, <i>prmt1</i> depletion in muscles specifically impaired TBK1 (TANK binding kinase 1)-OPTN (optineurin)-mediated mitophagy. Overall, our findings suggest that PRMT1 plays a critical role in maintaining NMJ and mitochondrial health by regulating selective mitophagy through TBK1-OPTN.<b>Abbreviations:</b> ADMA: asymmetric arginine dimethylation; BTX: α-bungarotoxin; EDL: extensor digitorum longus; FDB: flexor digitorum brevis; GAS: gastrocnemius; NMJ: Neuromuscular junction; Mko: mice with muscle-specific <i>prmt1</i> ablation; MTOR: mechanistic target of rapamycin kinase; OPTN: optineurin; PRMT1: protein arginine methyltransferase 1; SA: sodium arsenate; SNI: sciatic nerve crush injury; Sol: soleus; SQSTM1/p62: sequestosome 1; TBK1: TANK binding kinase 1; TOMM20: translocase of outer mitochondrial membrane 20; TA: tibialis anterior; VDAC1: voltage dependent anion channel 1.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-18"},"PeriodicalIF":14.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982248","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":"EPG-5 regulates TGFB/TGF-β and WNT signalling by modulating retrograde endocytic trafficking.","authors":"Chongzhen Yuan, Huachuan Dong, Chunyan Wu, Jinyang Liu, Zheng Wang, Xingwei Wang, Haiyan Ren, Zhaoyu Wang, Qun Lu","doi":"10.1080/15548627.2025.2485420","DOIUrl":"10.1080/15548627.2025.2485420","url":null,"abstract":"<p><p>The Vici syndrome protein EPG5 acts as a tethering factor determining the fusion specificity of autophagosomes with late endosomes/lysosomes. Here we demonstrated that during <i>C. elegans</i> development, EPG-5 modulates SMA and MAB TGFB/TGF-β signaling in controlling body size and also WNT signaling in regulating cell migration. EPG-5 is required for retrograde trafficking of the TGFB receptor SMA-6 and WLS/Wntless homolog MIG-14. In <i>epg-5</i> mutants, SMA-6 and MIG-14 are trapped within hybrid endosomal structures, which colocalize with SNX-1- and SNX-3-labeled vesicles, respectively. Basolateral recycling processes of transmembrane cargos H.s.TFR/hTfR and H.s.IL2RA/hTAC are also defective in <i>epg-5</i> mutants. Depletion of EPG-5 causes defective RAB-5 and RAB-7, and RAB-5 and RAB-10 conversion, leading to the formation of these hybrid vesicles. The defects in endocytic trafficking and autophagy in <i>epg-5</i> mutants are ameliorated by knocking down components of the HOPS complex. Our study demonstrates the intersection between the autophagy pathway and the endocytic pathway, providing insights into the pathogenesis of amyotrophic lateral sclerosis (ALS) and Vici syndrome.<b>Abbreviations:</b> ALM: anterior lateral microtubule; ATG: autophagy related; AVM: anterior ventral microtubule; CORVET: class C core vacuole/endosome tethering; DAF-4: abnormal dauer formation 4; DIC: differential interference contrast; EPG: ectopic PGL granules; EPG-5: ectopic P granules 5; GAP: GTPase activating protein; GFP: green fluorescent protein; HOPS: homotypic fusion and vacuole protein sorting; H.s.IL2RA/hTAC: human interleukin 2 receptor subunit alpha; H.s.TFR/hTfR: human transferrin receptor; L1/L4: the first/fourth larval; mCh: mCherry; MIG-14: abnormal cell migration 14; PLM: posterior lateral microtubule; PVM: posterior ventral microtubule; RAB: ras-related protein; RFP: red fluorescent protein; RME-1: receptor mediated endocytosis 1; SMA-6: small 6; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SNX: sorting nexin; TBC-2: TBC1 (Tre-2/Bub2/Cdc16) domain family 2; TGFB/TGF-β: transforming growth factor beta; TGN: trans-Golgi network; VPS: related to yeast vacuolar protein sorting factor; WT: wild type.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1995-2008"},"PeriodicalIF":14.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733602","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}

{"title":"Overlapping functions between <i>Lamp2a</i> and <i>Lamp2b</i> in cardiac autophagy.","authors":"Marina Sampaio Cruz, Ana Maria Manso, Angel Soto-Hermida, Paul Bushway, Elizabeth Silver, Betul Beyza Gunes, Zhiyuan Tang, Giovanni Gonzalez, Sharon Lau, Jordan Arbayo, Rita H Najor, Liguo Chi, Yusu Gu, Wei Feng, Randy T Cowling, Asa B Gustafsson, Ju Chen, Eric D Adler","doi":"10.1080/15548627.2025.2484620","DOIUrl":"10.1080/15548627.2025.2484620","url":null,"abstract":"<p><p>LAMP2 is a ubiquitously expressed protein critical for autophagy. Alternative splicing gives rise to three isoforms. However, the roles of major LAMP2 isoforms in the heart are not known. To address this knowledge gap, we generated <i>lamp2a</i> and <i>lamp2b</i> knockout (KO) mice to investigate the role of these isoforms in heart function and autophagy. Deletion of either <i>Lamp2a</i> or <i>Lamp2b</i> did not alter cardiac structure or function. Lack of all LAMP2 isoforms led to increased cardiac fibrosis and reduced survival during pressure overload, which were not observed in <i>lamp2a</i> or <i>lamp2b</i> KO mice. Also, LAMP2B loss did not affect levels of the autophagy markers LC3-II and SQSTM1/p62. Conversely, LAMP2A was upregulated in hearts lacking LAMP2B, potentially preserving autophagy and cardiac function. Reintroducing LAMP2A in <i>lamp2</i> KO mice effectively reduced autophagosome accumulation and improved cardiac function. Overall, these data support LAMP2 isoform functional redundancy in the myocardium under pathological conditions.<b>Abbreviations</b>: AAV: adeno-associated virus; ACTA2: actin alpha 2, smooth muscle, aorta; CMA: chaperone-mediated autophagy; KO: knockout; LAMP2: lysosomal-associated membrane protein 2; LV: Left ventricle; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; NPPA: natriuretic peptide type A; NPPB: natriuretic peptide type B; SQSTM1/p62: sequestosome 1; PBS: phosphate-buffered saline; PCR: polymerase chain reaction; TAC: transverse aortic constriction; WT: wild type.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"2046-2057"},"PeriodicalIF":14.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813214","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}

{"title":"N-degron-mediated ATG8 isoform switching controls plant thermotolerance.","authors":"Seu Ha Kim, Ohkmae K Park","doi":"10.1080/15548627.2025.2552904","DOIUrl":"https://doi.org/10.1080/15548627.2025.2552904","url":null,"abstract":"<p><p>Macroautophagy/autophagy is a highly conserved catabolic pathway in eukaryotes that mediates the selective degradation and recycling of cellular components through the formation of double-membrane autophagosomes. ATG8 is a core component of autophagy and determines cargo selectivity through interactions with specific cargo receptors. Higher plants harbor multiple ATG8 isoforms, implying potential functional diversification; however, the biological significance of this isoform expansion remains largely unexplored. In a recent study, we identified UBR7 (UBIQUITIN PROTEIN LIGASE E3 COMPONENT N-RECOGNIN 7) as a novel N-recognin that targets ATG8a for proteasomal degradation via the Arg/N-degron pathway. This selective degradation triggers isoform switching by enabling the replacement of ATG8a with alternative ATG8 isoforms. Notably, this process occurs specifically during the recovery phase following heat stress and plays a critical role in enhancing thermotolerance. Our findings provide new insights into the functional specialization and dynamic regulation of ATG8 isoforms in plants and suggest new directions for improving crop resilience under climate-associated temperature fluctuations.<b>Abberivations</b> HS, heat stress: HSP, heat shock protein; RBP, RNA-binding protein; UTR, untranslated region.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-3"},"PeriodicalIF":14.3,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982274","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":"Deacetylation of ATG16L1 is required for LC3-associated lysosomal microautophagy.","authors":"Qian Wang, Wei Wan, Hongtao Zhang, Tianhua Zhou, Han-Ming Shen, Pingtong Huang, Wei Liu","doi":"10.1080/15548627.2025.2551669","DOIUrl":"https://doi.org/10.1080/15548627.2025.2551669","url":null,"abstract":"<p><p>Microautophagy is a selective cellular process in which endolysosomes directly engulf cytoplasmic cargo through membrane invagination. The regulatory mechanisms governing microautophagy remain poorly understood. Here, we identified the deacetylation of ATG16L1 as a critical regulator of LC3-associated lysosomal microautophagy. We demonstrate that ATG16L1 acetylation is dynamically controlled by the acetyltransferase KAT2B and the deacetylase HDAC3. Under lysosomal osmotic stress or glucose deprivation, HDAC3-mediated deacetylation of ATG16L1 within its WD40 domain promotes its interaction with V-ATPase, facilitating ATG16L1 recruitment to lysosomal membranes. While dispensable for macroautophagy, this post-translational modification is essential for LC3 lipidation on lysosomes and enables lysosomal recovery, including the restoration of lysosomal size and degradative capacity following stress. Our results reveal a key role for ATG16L1 deacetylation in driving LC3-associated microautophagy to maintain lysosomal homeostasis.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-15"},"PeriodicalIF":14.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982298","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":"<i>Salmonella</i> Typhimurium exploits the reticulophagy/ERphagy receptor RETREG1 to promote infection.","authors":"Damian Gatica, Reham Alsaadi, Ryan C Russell","doi":"10.1080/15548627.2025.2551672","DOIUrl":"https://doi.org/10.1080/15548627.2025.2551672","url":null,"abstract":"<p><p>Macroautophagy/autophagy is a key catabolic-recycling pathway that can selectively target damaged organelles or invading pathogens for degradation. The selective autophagic degradation of the endoplasmic reticulum, called reticulophagy/ERphagy, controls ER size and degradation of misfolded protein aggregates. RETREG1/FAM134B is an ERphagy receptor that acts by inducing ER membrane curvature and scission through oligomerization. Interestingly, RETREG1 has also been implicated in the cellular response against pathogen infection. Multiple microbes have developed strategies to inhibit ERphagy by targeting RETREG1. In a recent study, we characterized an unidentified mechanism of bacterial-mediated inhibition of ERphagy. Specifically, we found that <i>Salmonella enterica</i> Serovar Typhimurium, a well-known intracellular pathogen that continues to be a major cause of foodborne infections worldwide, inhibits ERphagy by specifically targeting the activity of RETREG1, leading to a pronounced increase in <i>Salmonella</i> burden. We show that <i>Salmonella</i> prevents RETREG1 oligomerization, which is required for efficient ERphagy. Conversely, <i>Salmonella</i>-mediated ERphagy blockage can be bypassed by promoting RETREG1 oligomerization, which recovers ERphagy levels. <i>Salmonella</i> infection also decreases RETREG1 phosphorylation and acetylation, previously reported to be requisite steps in RETREG1-driven ERphagy. Furthermore, in vivo analysis of <i>retreg1</i> knockout mice infected with <i>Salmonella</i> reveals increased intestinal damage and bacterial levels. Our results provide insights into the interplay between ERphagy and bacterial infection, highlighting a key role for RETREG1 in innate immunity.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-3"},"PeriodicalIF":14.3,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982284","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}