Autophagy最新文献

{"title":"Physiological insights into ESCRT-mediated phagophore closure: potential cytoprotective roles for ATG8ylated membranes.","authors":"Kouta Hamamoto, Xinwen Liang, David M Opozda, Hong-Gang Wang, Yoshinori Takahashi","doi":"10.1080/15548627.2025.2468907","DOIUrl":"10.1080/15548627.2025.2468907","url":null,"abstract":"<p><p>The endosomal sorting complex required for transport (ESCRT) machinery is a membrane abscission system that mediates various intracellular membrane remodeling processes, including macroautophagy/autophagy. In our recent study, we established the unique requirement of the ubiquitin E2 variant-like (UEVL) domain of the ESCRT-I subunit VPS37A for phagophore closure, the final step in autophagosome biogenesis, and determined the physiological impact of systemically inhibiting closure by targeting this region in mice. While the mutant mice exhibited phenotypes similar to those reported in mice deficient in generating ATG8 (mammalian Atg8 homologs)-conjugated (ATG8ylated) phagophores, certain phenotypes, such as neonatal lethality and liver injury, were found to be notably milder. Further investigation revealed that ATG8ylated phagophores promote TBK1-dependent SQSTM1 phosphorylation and droplet formation, leading to the formation of large insoluble aggregates upon closure inhibition. These findings suggest potential roles for ATG8ylated membranes in mitigating proteotoxicity by efficiently concentrating and sequestering soluble, reactive microaggregates and converting them into less reactive, insoluble large aggregates. The study highlights VPS37A UEVL mutant mice as a model for investigating the physiological and pathological roles of phagophores that extend beyond degradation.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1387-1389"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461067","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":"SESN1 negatively regulates STING1 to maintain innate immune homeostasis.","authors":"Lingxiao Xu, Hongqian Zhang, Zuocheng Qiu, Shijing Wang, Chaoyang Wang, Hao Cheng, Qianya Wan, Mingyu Pan","doi":"10.1080/15548627.2025.2463148","DOIUrl":"10.1080/15548627.2025.2463148","url":null,"abstract":"<p><p>STING1 is a central hub protein of CGAS-STING1 signaling which is important signaling axis to sense DNA for the host against pathogens infection through regulating type I interferon (IFN-I) production. However, excessive STING1 activation-induced overproduced IFN-I triggers tissue damage and autoimmune disorders. Thus, the activity of STING1 must be precisely regulated for immune homeostasis. Here, we discovered SESN1 (sestrin 1) as an essential negative regulator of STING1 to maintain immune homeostasis. Upon herpes simplex virus-1 (HSV-1) infection, the expression of SESN1 was downregulated, which enhanced potentiality to virus defense for host. Consistently, SESN1-deficient mice exhibited stronger ability against HSV-1 infection compared to wild-type littermates. Additionally, we found the expression of SESN1 was decreased in systemic lupus erythematosus (SLE) patients and <i>trex1</i> KO mouse model of autoimmune disease. Intriguingly, the replenishment of SESN1 effectively impressed IFN-I production and autoimmune responses in the PBMCs of human SLE specimens and the <i>trex1</i> KO mouse model both <i>in vitro</i> and <i>in vivo</i>. Mechanistically, SESN1 targeted STING1 and promoted STING1 autophagic degradation by facilitating the interaction of SQSTM1/p62 and STING1. Together, our study uncovers a crucial role of SESN1 for immune homeostasis to balance anti-virus and autoimmunity by regulating STING1. SESN1 might be a potential therapeutic target for infectious and autoimmune diseases.<b>Abbreviations</b>: BMDMs: bone marrow-derived macrophages; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; HTDNA: herring testes DNA; IFNA4: interferon alpha 4; IFNB: interferon beta; IRF3: interferon regulatory factor 3; ISD: interferon stimulatory DNA; ISGs: IFN-stimulated genes; PBMCs: peripheral blood mononuclear cells; RSAD2: radical S-adenosyl methionine domain containing 2; SLE: systemic lupus erythematosus; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1245-1262"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411856","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":"S-palmitoylation coordinates the trafficking of ATG9A to mediate autophagy initiation.","authors":"Fan Xia, Weining Li, Wenru Wang, Jiru Liu, Xiaolin Li, Jing Cai, Hao Shan, Zhe Cai, Jun Cui","doi":"10.1080/15548627.2025.2509376","DOIUrl":"10.1080/15548627.2025.2509376","url":null,"abstract":"<p><strong>Abbreviation: </strong>17-ODYA: 17-octadecynoic acid; 293T: HEK293T; 2-BP: 2-bromopalmitate; 2CS: Cys155Ser and Cys156Ser; ABE: acyl-biotin exchange; AP: adaptor protein; APEX2: ascorbate peroxidase 2; ATG: autophagy related; baf A₁: bafilomycin A₁; CRISPR: clustered regularly interspaced short palindromic repeats; CTD: C-terminal domain; Cys: cysteine; DAB: 3,3'-diaminobenzidine; EV: empty vector; H₂O₂: hydrogen peroxide; IF: immunofluorescence; IP: immunoprecipitation; KO: knockout; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; NTD: N-terminal domain; PAS: phagophore assembly site; PBS: phosphate-buffered saline; PtdIns3K-CI: class III phosphatidylinositol 3-kinase complex I; PM: plasma membrane; PTM: post-translational modifications; Ser: serine; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TGN: trans-Golgi network; ULK1: unc-51 like autophagy activating kinase 1; WCL, whole cell lysates; WDR45/WIPI4: WD repeat domain 45; WT: wild-type; ZFYVE1/DFCP1: zinc finger FYVE-type containing 1.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-21"},"PeriodicalIF":0.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112994","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 pathway of autophagy in the epigenetic landscape of <i>Mycobacterium</i>-host interactions.","authors":"Abhishek Mishra, Varsha Rawat, Kangling Zhang, Chinnaswamy Jagannath","doi":"10.1080/15548627.2025.2511074","DOIUrl":"10.1080/15548627.2025.2511074","url":null,"abstract":"<p><p>Macroautophagy (autophagy) is an evolutionarily conserved process that degrades excess cytoplasmic components, such as protein aggregates and damaged organelles, by encapsulating them within double-membrane autophagosomes. These autophagosomes undergo distinct stages - initiation, phagophore nucleation, expansion, and closure - before fusing with lysosomes (or occasionally endosomes) for degradation and recycling. This process is regulated by ATG (autophagy related) proteins, which govern autophagosome formation and lysosomal fusion. Epigenetic modifications and transcription factors can regulate <i>ATG</i> gene expression in the nucleus. Autophagy also plays a key role in eliminating intracellular <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) through the lytic and antimicrobial activities of autolysosomes, which are more potent antimicrobial compartments than conventional phagosomes. Emerging evidence suggests that <i>Mtb</i> can modify the host epigenome and transcriptional machinery, significantly affecting the host immune response. This review explores the epigenetic regulation of autophagy during mycobacterium-host interactions. The interplay between epigenetic regulation and autophagy highlights a crucial aspect of host-pathogen interactions during <i>Mtb</i> infection. Understanding how <i>Mtb</i> manipulates the host epigenome to regulate autophagy could lead to the development of novel therapeutic strategies that enhance autophagic pathways or counteract <i>Mtb's</i> immune evasion tactics.<b>Abbreviations</b>: AM: Alveolar macrophages; ATG: autophagy related; DNMT: DNA methyltransferase; FOXO3: forkhead box O3; HAT: histone acetyltransferase; HDAC: histone deacetylase; MIR: microRNA; MTOR: mechanistic target of rapamycin kinase; <i>Mtb</i>: Mycobacterium tuberculosis; ROS: reactive oxygen species; SIRT: sirtuin; STPK: serine/threonine protein kinase.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-19"},"PeriodicalIF":0.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144846","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":"Autophagic degradation of SQSTM1 enables fibroblast activation to accelerate wound healing.","authors":"Yujiao Xu, Xin Gu, Wenshu Li, Boyang Lin, Yiting Xu, Qingcheng Wei, Qingyuan Liu, Yamin Zhao, Rongzhuo Long, Hulin Jiang, Zhaoqiu Wu, Yunyao Liu, Lei Qiang","doi":"10.1080/15548627.2025.2508546","DOIUrl":"10.1080/15548627.2025.2508546","url":null,"abstract":"<p><p>Wound healing is a meticulously coordinated and intricate progression that necessitates precise regulation of fibroblast behavior. Macroautophagy/autophagy is a degradation system for clearing damaged cellular components. SQSTM1/p62 (sequestosome 1), a well-established autophagy receptor, also functions as a signaling hub beyond autophagy. Here, we observed a significant upregulation of autophagy in fibroblasts after wounding. Using mice with fibroblast-specific deletion of <i>Atg7</i> (autophagy related 7), we found that fibroblast autophagy governed wound healing. Fibroblast autophagy deficiency delayed proper dermal repair that was mired in insufficient fibroblast proliferation, migration, and myofibroblast transition. <i>In vitro</i> experiments further revealed that autophagy deficiency disrupted TGFB1 (transforming growth factor beta 1)-induced fibroblast proliferation, migration, and myofibroblast differentiation. Mechanistically, autophagy deficiency led to SMAD2 (SMAD family member 2) and SMAD3 sequestration within SQSTM1 bodies and attenuated TGFB1-induced receptor-regulated SMAD (R-SMAD) phosphorylation in an SQSTM1-dependent manner. Furthermore, <i>sqstm1</i> deletion rescued the delayed skin wound healing caused by autophagy deficiency, and autophagy inducers promoted wound healing in an SQSTM1-dependent manner. Our findings highlight the critical role of fibroblast autophagy in wound healing and elucidate the underlying mechanisms by which autophagy regulates fibroblast behavior.<b>Abbreviation</b>: 3-MA: 3-methyladenine; ACTA2/α-SMA: actin alpha 2, smooth muscle; ACTB: actin beta; AMPK: AMP-activated protein kinase; ATG: autophagy related; BiFC: bimolecular fluorescence complementation; COL1A2: collagen type I alpha 2 chain; ECM: extracellular matrix; FGF: fibroblast growth factor; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HDF: human dermal fibroblast; HVGs: highly variable genes; KO: knockout; LMNB1: lamin B1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MKI67/Ki-67: marker of proliferation Ki-67; MTOR/mTOR: mechanistic target of rapamycin kinase; NFE2L2/NRF2: NFE2 like bZIP transcription factor 2; NFKB: nuclear factor kappa B; NLRP3: NLR family pyrin domain containing 3; PCA: principal component analysis; PI3K: phosphoinositide 3-kinase; R-SMAD: receptor-regulated SMAD; SBE: SMAD binding element; shCON: small hairpin negative control; siNC: negative control; siRNA: small interfering RNA; SMAD: SMAD family member; SQSTM1/p62: sequestosome 1; ssGSEA: single-sample gene set enrichment analysis; TGFB/TGF-β: transforming growth factor beta; TGFBR1: transforming growth factor beta receptor 1; TGFBR2: transforming growth factor beta receptor 2; VIM: vimentin; WT: wild-type; ZFYVE9/SARA: zinc finger FYVE-type containing 9.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-21"},"PeriodicalIF":0.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121630","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":"Epilepsy and autophagy modulators: a therapeutic split.","authors":"Hayder M Al-Kuraishy, Majid S Jabir, Ali I Al-Gareeb, Ali K Albuhadily, Daniel J Klionsky, Mayyadah F Rafeeq","doi":"10.1080/15548627.2025.2506292","DOIUrl":"10.1080/15548627.2025.2506292","url":null,"abstract":"<p><p>Epilepsy is a neurological disease characterized by repeated unprovoked seizure. Epilepsy is controlled by anti-epileptic drugs (AEDs); however, one third of epileptic patients have symptoms that are not controlled by AEDs in a condition called refractory epilepsy. Dysregulation of macroautophagy/autophagy is involved in the pathogenesis of epilepsy. Autophagy prevents the development and progression of epilepsy through regulating the balance between inhibitory and excitatory neurotransmitters. Induction of autophagy and autophagy-related proteins could be a novel therapeutic strategy in the management of epilepsy. Despite the protective role of autophagy against epileptogenesis and epilepsy, its role in status epilepticus is perplexing and might reflect its nature as a double-edged sword. Autophagy inducers play a critical role in reducing seizure frequency and severity, and could be an adjuvant treatment in the management of epilepsy. However, autophagy inhibitors also have an anticonvulsant effect. Therefore, the aim of the present mini-review is to discuss the potential role of autophagy in the pathogenesis of epileptogenesis and epilepsy, and how autophagy modulators affect epileptogenesis and epilepsy.<b>Abbreviations:</b> AD: Alzheimer disease; AEDs: antiepileptic drugs; AMPK: adenosine monophosphate-activated protein kinase; ER: endoplasmic reticulum; GABA: gamma aminobutyric acid; HCQ: hydroxycholoroquine; IP₃: inositol 1,4,5-trisphosphate; NSAID: non-steroidal anti-inflammatory drug; PI3K: phosphoinositide 3-kinase; ROS: reactive oxygen species; SE: status epilepticus; PTZ: pentylenetetrazole; TLE: temporal lobe epilepsy; TSC: tuberous sclerosis complex.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-25"},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082728","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":"Defective autophagy in a fibroin secretion-deficient silkworm mutant.","authors":"Jianhua Xia, Haiqin Chen, Yuying Wang, Wenbo Hu, Kaiyu Guo, Qingqing Linghu, Pengchao Guo, Xin Wang, Qingyou Xia, Ioannis P Nezis, Ping Zhao, Zhaoming Dong, Yan Zhang","doi":"10.1080/15548627.2025.2510843","DOIUrl":"10.1080/15548627.2025.2510843","url":null,"abstract":"<p><p>The silkworm <i>Bombyx mori</i> is an economically important insect for silk production. Its silk glands are responsible for the synthesis and secretion of silk proteins. The naked pupa (<i>Nd</i>), a fibroin heavy chain mutant strain of silkworm, was found to exhibit severe atrophy, degeneration of the posterior silk gland (PSG), and abnormal secretion of fibroin proteins, thereby producing little or no silk. Here, we found that the autophagic marker Atg8-PE was upregulated through the target of rapamycin complex 1 signaling pathway in <i>Nd</i>. However, as autophagy substrates, SQSTM1/p62 and ubiquitinated protein levels increased in <i>Nd</i>. Furthermore, treatment with BafA1 showed no effect on the protein levels of SQSTM1/p62, indicating impaired autophagic flux in <i>Nd</i>. Abnormal acidification of lysosomes was further detected, which resulted in a decreased proportion of matured CtsL1 (cathepsin L1). Thus, the substrate in autolysosomes cannot be degraded within a rapid time frame, resulting in the accumulation of protein aggregates, which cause atrophy and degeneration of the PSG. We also found that acidic nanoparticles rescued lysosomal acidification and relieved the degenerative changes of <i>Nd</i>-PSG. The findings of this study suggest that the <i>Nd</i> mutant silkworm can be used as an animal model for studying protein aggregation diseases.<b>Abbreviations</b>: AD: Alzheimer disease; aNP: acidic nanoparticle; APP: amyloid beta precursor protein; Atg8: autophagy related 8; BACE1: beta-secretase 1; BafA1: bafilomycin A₁; CtsL1: cathepsin L1; CRY: crystallin; ER: endoplasmic reticulum; FibH: fibroin heavy chain; FibL: fibroin light chain; FUS: FUS RNA binding protein; HD: Huntington disease; HRP: horseradish peroxidase; <i>Nd</i>: naked pupa; OSBPL2: oxysterol binding protein like 2; PD: Parkinson disease; PE: phosphatidylethanolamine; p-EIF4EBP: phosphorylated eukaryotic initiation factor 4E binding protein; PROM1: prominin 1; p-RPS6KB: phosphorylated ribosomal protein S6 kinase B; PSEN: presenilin; PSG: posterior silk gland; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SEM: standard error of the mean; SOD1: superoxide dismutase 1; SQSTM1/p62: sequestosome 1; TARDBP: TAR DNA binding protein; TORC1: target of rapamycin complex 1; UBQLN2: ubiquilin 2; V-ATPase: vacuolar-type ATPase.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144903","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":"MCOLN1/TRPML1-MCOLN3/TRPML3 heteromer and its coupling to Ca²⁺ sensor SYT5 regulates autophagosome-lysosome fusion in a PtdIns4P-dependent manner.","authors":"Jin Kwon, So Woon Kim, Seokwoo Hong, Areum Choi, Suzi Choi, Myoung Kyu Park, Hyun Jin Kim","doi":"10.1080/15548627.2025.2510846","DOIUrl":"10.1080/15548627.2025.2510846","url":null,"abstract":"<p><p>Macroautophagy/autophagy progresses through Ca²⁺-dependent multiple fusion events. Recently, we reported that the intracellular Ca²⁺ channel MCOLN3/TRPML3 provides Ca²⁺ for membrane fusion during autophagosome formation as a downstream effector of phosphatidylinositol-3-phosphate (PtdIns3P). However, the molecular mechanism of Ca²⁺ signaling in the late stage of autophagy remains unknown. Here, we show that the MCOLN1/TRPML1-MCOLN3/TRPML3 heteromer is the Ca²⁺ provider for autophagosome-lysosome fusion. MCOLN1-MCOLN3 functions downstream of PtdIns4P to release Ca²⁺ from autophagosomes, and the Ca²⁺ signal via PtdIns4P-MCOLN1-MCOLN3 is decoded by the Ca²⁺ sensor SYT5 (synaptotagmin 5). The binding of Ca²⁺ and PtdIns4P to SYT5 is critical for autophagosome-lysosome fusion by forming a fusion complex. Collectively, these results reveal that PtdIns4P-MCOLN1-MCOLN3-SYT5 constitutes the Ca²⁺ signaling complex in autophagosome-lysosome fusion and that MCOLN3 also regulates the late stage of autophagy through heteromerization with MCOLN1 in a phosphoinositide (PI)-dependent manner.<b>Abbreviations</b>: ATG, autophagy related; CPA, cyclopiazonic acid; DN, dominant-negative; GPN, glycyl-L-phenylalanine-beta-naphthylamide; KO, knockout; NH₄Cl, ammonium chloride; PtdIns3K, phosphatidylinositol 3-kinase; PtdIns3P, phosphatidylinositol-3-phosphate; PI, phosphoinositide; SYT5, synaptotagmin 5; tfLC3, mRFP-GFP tandem fluorescent-tagged LC3; WT, wild-type.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-17"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144845","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 plays a dual role in chromoplast transition and degradation and is essential for fruit coloration and ripening.","authors":"Ye Guo, Zhiru Bao, Meiyan Shi, Qiwei Zheng, Yawen Huo, Ran Hu, Yajie Guan, Saiyu Cao, Patrick J Hussey, Xiuxin Deng, Yunjiang Cheng, Pengwei Wang","doi":"10.1080/15548627.2025.2509330","DOIUrl":"10.1080/15548627.2025.2509330","url":null,"abstract":"<p><p>The color of tomato fruits is determined by carotenoids. The process involves removing chloroplast-related components and the biogenesis of chromoplast membranes where carotenoids are stored, but how these events are coordinated is unknown. Here, we demonstrated that part of this mechanism involves macroautophagy/autophagy playing dual roles in chromoplast transition and degradation. We have used fluorescence lifetime imaging microscopy (FLIM) to show that autophagosomes containing chloroplast-derived-vesicles increased significantly during early fruit ripening, which is an essential part of a pathway to the formation of chromoplasts. Interestingly, we also showed that autophagy controls the degradation of the chromoplasts containing carotenoids at the late ripening stage through a process we named chromophagy. This affects fruit color and ABA levels, which were higher in autophagy mutants with a slower turnover of chromoplasts. We concluded that autophagy is a determinant of both fruit coloration and ripening through degrading different plastid-related cargo.<b>Abbreviation</b>: ABA: abscisic acid; ATG: autophagy related; AP: autophagosome; BR: breaker stage; BR + 3: 3 days after breaker stage; BR + 7: 7 days after breaker stage; CV: coefficient of variation; FLIM: fluorescence lifetime imaging microscopy; IG: immature green; LR: light red; MG: mature green; PDVs: plastid-derived-vesicles; RhB: rhodamine B; RNAi: RNA interference; RR: ripe red; TEM: transmission electron microscopy; WLL: white-light laser.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112991","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":"ATG5 controls CD80 expression in B cells and shapes cognate CD4⁺ T cell responses.","authors":"Ingredy Passos, Thomas Zobel, Christian Münz, Anneli Peters, Jan D Lünemann","doi":"10.1080/15548627.2025.2507614","DOIUrl":"https://doi.org/10.1080/15548627.2025.2507614","url":null,"abstract":"<p><p>The macroautophagy/autophagy machinery has been implicated in supporting MHC class II but compromising MHC class I restricted antigen presentation by dendritic cells (DCs). Here, we report that loss of the essential autophagy protein ATG5 in B cells reduces internalization and stabilizes co-stimulatory CD80 surface expression. In an adjuvant-free experimental autoimmune encephalomyelitis (EAE) mouse model, co-transfer of MOG-specific induced germinal center B (iGB) cells deficient in ATG5 with MOG-specific CD4⁺ T cells, accelerated disease development. CD80 blockade abrogated enhanced cognate CD4⁺ T-cell responses induced by iGB cells lacking ATG5. These data broaden the concept of ATG5-mediated antigen presentation and indicate that ATG5 might not only enhance, as described previously with MHC class II-restricted presentation in DCs, but also limit the activation of CD4⁺ T cells through attenuating CD80 expression on B cells.<b>Abbreviations</b>: APC: antigen-presenting cell; CNS: central nervous system; DC: dendritic cell; EAE: experimental autoimmune encephalomyelitis; iGB: induced germinal center B cell; MOG: myelin oligodendrocyte glycoprotein; MS: multiple sclerosis.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164301","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}