Autophagy reports最新文献

{"title":"Rethinking autophagy during odontogenesis through autophagic flux.","authors":"Bruno Calsa, Patrícia Aline Boer","doi":"10.1080/27694127.2026.2748072","DOIUrl":"https://doi.org/10.1080/27694127.2026.2748072","url":null,"abstract":"<p><p>Tooth development requires precise coordination of proliferation, differentiation, and tissue remodeling. Although macroautophagy/autophagy has been implicated in odontogenesis, its dynamic regulation during embryonic tooth development remains poorly understood because previous studies relied primarily on static markers. In our recent study, we analyzed autophagic flux in mouse tooth germs using a tandem fluorescent reporter of microtubule associated protein 1 light chain 3 (LC3) combined with lysosomal associated membrane protein 1 (LAMP1) immunostaining and found that gestational protein restriction altered the autophagic vesicle profile in a stage- and compartment-specific manner. The most pronounced alterations occurred at the bud stage and coincided with reduced cell proliferation and increased apoptosis. These findings suggest that early odontogenesis is a particularly vulnerable window in which efficient and properly timed autophagic flux may be required for morphogenesis. Because tandem reporters cannot distinguish canonical autophagy from non-degradative LC3-dependent pathways, we also discuss this limitation and raise new questions about the role of autophagy in epithelial-mesenchymal interactions.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2748072"},"PeriodicalIF":0.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149240433","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":"TRPML3 and TRPML1/3 differentially regulate unconventional MIF secretion through TMED10 and secretory autophagy.","authors":"Jiwoo Park, Jin Kwon, Suzi Choi, Hyun Jin Kim","doi":"10.1080/27694127.2026.2740425","DOIUrl":"https://doi.org/10.1080/27694127.2026.2740425","url":null,"abstract":"<p><p>The intracellular Ca²⁺ channel TRPML3 regulates autophagy by multimerization in a phosphoinositide (PIP)-dependent manner; however, its role in other membrane dynamics remains unclear. Here, we report that TRPML3 regulates type III unconventional protein secretion (UcPS) through two distinct pathways: TMED10-channeled UcPS and secretory autophagy. TRPML3 interacted with TMED10 and macrophage migration inhibitory factor (MIF), a signal sequence-lacking pleiotropic cytokine whose secretion mechanism has remained undefined. We found that cytosolic MIF is transported to membrane-enclosed compartments through TMED10-channeled UcPS. Notably, TRPML3, but not TRPML1 or TRPML1/3, promoted TMED10 oligomerization, thereby enhancing MIF secretion in a Ca²⁺-independent manner. Furthermore, once translocated into vesicular compartments, MIF colocalized with LC3, and its secretion was dependent on secretory autophagy. Mechanistically, we identified PI(3,4)P₂ as a key regulator of secretory autophagy, with TRPML1/3 acting downstream of PI(3,4)P₂ to mediate Ca²⁺-dependent MIF secretion. Taken together, our findings demonstrate that MIF is a novel cargo of type III UcPS, operating through TMED10-channeled UcPS and secretory autophagy, which are regulated by TRPML3 in a Ca²⁺-independent manner and by the PI(3,4)P₂-TRPML1/3 axis in a Ca²⁺-dependent manner, respectively.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2740425"},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170532","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":"LC3-associated phagocytosis is impaired in monocyte-derived macrophages from systemic sclerosis patients.","authors":"Quentin Frenger, Julie Lucas, Arthur Petitdemange, Luisa Path, Nadège Wadier, Sabine Depauw, Stéphane Giorgiutti, Yazhuo Gong, Hélène Merlin, Aurore Meyer, Mathilde Herber, Léa Jaquel, Philippe Mertz, Renaud Felten, Emmanuel Chatelus, Yannick Dieudonne, Aurélien Guffroy, Laurent Arnaud, Vincent Poindron, Jacques-Eric Gottenberg, Jean Sibilia, Anne-Sophie Korganow, Thierry Martin, Frédéric Gros","doi":"10.1080/27694127.2026.2730912","DOIUrl":"10.1080/27694127.2026.2730912","url":null,"abstract":"<p><p>Autophagy-related (ATG) proteins orchestrate canonical autophagy and related pathways, including LC3-associated phagocytosis (LAP). Autophagy and LAP play essential roles in immune homeostasis and regulation. Systemic sclerosis (SSc) is an autoimmune disease of unknown etiology characterized by progressive fibrosis affecting the skin and multiple internal organs, together with profound immune dysregulation. <i>ATG</i> alleles have been proposed as genetic susceptibility factors for SSc, suggesting that defects in autophagy-related pathways may contribute to the disease pathogenesis. We investigated whether canonical autophagy and/or LAP are altered in immune cells from patients with SSc. Autophagy was assessed by measuring LC3-II levels in circulating cells from SSc patients and controls, and autophagic flux was evaluated by flow cytometry following lysosomal inhibition. We then generated monocyte-derived macrophages and performed phagocytosis assays to assess the LAP activity. We evaluated the phagocytic capacity using IgG-coated beads that trigger LAP through Fcγ receptor engagement and measured the proportion of LC3-positive phagosomes (LAPosomes). No major defects in canonical autophagy were found in lymphocytes and monocytes isolated from the peripheral blood of patients with SSc. In contrast, monocyte-derived M0 macrophages from patients with SSc exhibited impaired LC3-associated phagocytosis. Impaired LAP in macrophages may contribute to the defective efferocytosis observed in SSc, thereby promoting persistent inflammation and fibrosis. Our findings identify LAP as a previously unrecognized pathway altered in SSc and suggest that therapeutic strategies aimed at restoring LAP activity may represent a novel approach for disease treatment.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2730912"},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139239","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":"Multilayered interplay between the cGAS-STING pathway and autophagy.","authors":"Ze-Bo Huang, Xiang-Zheng Gao, Jin-Yi Lin, Du Feng, Guang Lu","doi":"10.1080/27694127.2026.2728537","DOIUrl":"10.1080/27694127.2026.2728537","url":null,"abstract":"<p><p>The cGAS-STING pathway detects cytosolic dsDNA to initiate innate immune responses, serving as a critical surveillance system against infection and cellular stress. Autophagy is an evolutionarily conserved catabolic process that maintains homeostasis by degrading cytoplasmic components. Although these two systems operate through distinct mechanisms, recent studies have uncovered a complex bidirectional regulatory network that intimately links them. On the one hand, STING has an evolutionarily conserved capacity to induce TBK1-independent noncanonical autophagy, and recent studies further link this activity to TFEB-dependent lysosome biogenesis, expanding its functional repertoire beyond classical interferon induction. On the other hand, autophagy restricts cGAS-STING signaling by clearing cytosolic DNA and selectively degrading pathway components, thereby preventing excessive inflammation. Furthermore, mitophagy curtails the release of mitochondrial DNA, a potent cGAS agonist, and recent studies further implicate lysosomes as active signaling platforms associated with mtDNA release, LRRK2 activation, and STING-dependent NF-κB responses. In this review, we discuss recent advances in understanding how the cGAS-STING pathway and autophagy mutually regulate each other at the cellular level, focusing on the molecular mechanisms of this interplay, both canonical and noncanonical, and highlighting how their crosstalk shapes cellular homeostasis and stress adaptation.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2728537"},"PeriodicalIF":0.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13577301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978936","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":"A <i>de novo VPS16</i> missense variant blocks autophagic flux and extends DYT-<i>VPS16</i> into infancy.","authors":"Enrique Gonzalez Saez-Diez, Xutong Xue, Darius Ebrahimi-Fakhari","doi":"10.1080/27694127.2026.2728539","DOIUrl":"10.1080/27694127.2026.2728539","url":null,"abstract":"<p><p>Autophagy terminates in the degradation of cargo delivered by fusion of the autophagosome with the lysosome, a step tethered by the homotypic fusion and vacuole protein sorting (HOPS) complex. Heterozygous loss-of-function variants in <i>VPS16</i>, which encodes a core HOPS subunit, cause autosomal dominant DYT-<i>VPS16</i> dystonia. The pathogenicity of missense alleles has remained uncertain due to a lack of mechanistic data from patient-derived cells. We summarize our recent report of the youngest individual with DYT-<i>VPS16</i> described to date. This child presented with infantile-onset generalized dystonia caused by a <i>de novo VPS16</i> missense variant, p. Ala466Thr. Patient-derived fibroblasts accumulate enlarged, stalled autolysosomes and show concurrent elevation of SQSTM1/p62 and the MAP1LC3B/LC3B-II:LC3B-I ratio, consistent with a block in autophagic flux. We discuss the consequences for variant interpretation, describe a previously unrecognized caudate-predominant neuroimaging correlate, and speculate on why striatal neurons are selectively vulnerable to HOPS dysfunction. <b>Abbreviations:</b> HOPS: homotypic fusion and vacuole protein sorting; LOF: loss-of-function; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; SQSTM1: sequestosome 1.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2728539"},"PeriodicalIF":0.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13568563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957363","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":"Correction.","authors":"","doi":"10.1080/27694127.2026.2727268","DOIUrl":"https://doi.org/10.1080/27694127.2026.2727268","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1080/27694127.2026.2685472.].</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2727268"},"PeriodicalIF":0.0,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921874","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":"Differential regulation of the proliferative and autophagic responses in murine and human pancreatic cancer cells.","authors":"Ruohong Wang, Albert Sw Sohn, Jiangwei Li, Mohamad Assi","doi":"10.1080/27694127.2026.2715823","DOIUrl":"10.1080/27694127.2026.2715823","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) cells rely on autophagy to adapt to microenvironmental stress. In our recent work, we showed that baseline autophagy flux levels shape the proliferative capacity of human PDAC cells. Here, we extend these findings by demonstrating that low baseline autophagy is consistently associated with enhanced proliferation <i>in vitro</i> and <i>in vivo</i> across multiple human and murine PDAC models. While this inverse relationship between autophagy flux and proliferation is conserved across species, the underlying regulatory mechanisms diverge. Namely, changes in baseline autophagy levels relied predominantly on canonical nutrient-sensing pathways in murine but not human PDAC cells. Additionally, we found that autophagy flux was regulated independently of the cell cycle or the genetic status of p53 (i.e., allelic deletion, point mutation). Collectively, our results reveal conserved phenotypic outcomes but divergent mechanisms, underscoring the need for parallel comparative approaches before extrapolating findings from mouse PDAC models to human disease.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2715823"},"PeriodicalIF":0.0,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851903","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":"Autophagy inhibition in pancreatic cancer: hope or hype?","authors":"Emma Guilbaud, Edna Cukierman, Igor Astsaturov, Lorenzo Galluzzi","doi":"10.1080/27694127.2026.2721748","DOIUrl":"10.1080/27694127.2026.2721748","url":null,"abstract":"<p><p>Autophagy promotes tumor progression and immune evasion by numerous mechanisms, representing a promising target for novel (immuno)therapeutic interventions in multiple oncological indications. An expanding literature, however, suggests that safely and effectively targeting autophagy in the clinic remains challenging, especially in populations as complex to manage as patients with pancreatic cancer.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2721748"},"PeriodicalIF":0.0,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13524002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851883","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":"A metabolic entry point into micro-chlorophagy: insights from impaired maltose metabolism.","authors":"Sakuya Nakamura, Shinya Hagihara, Masanori Izumi","doi":"10.1080/27694127.2026.2721027","DOIUrl":"10.1080/27694127.2026.2721027","url":null,"abstract":"<p><p>As the site of photosynthesis and carbohydrate metabolism, chloroplasts are essential for phototrophic plant growth. The selective elimination of damaged chloroplasts by autophagy, a process known as chlorophagy, is crucial for chloroplast quality control. However, the mechanisms that activate chlorophagy and that underline its specificity remain poorly understood. Our recent study identified changes in maltose metabolism as a previously unrecognized trigger of a micro-chlorophagy program that depends on components of the core autophagy machinery. These findings provide a new starting point for uncovering the molecular principles that govern micro-chlorophagy. Here, we discuss emerging evidence showing that metabolic changes induce autophagic chloroplast turnover and outline the key challenges in defining the signals that initiate micro-chlorophagy.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2721027"},"PeriodicalIF":0.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851925","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":"The role of N-glycans and their processing in ER-to-lysosome-associated degradation of disease-causing mutant Neuroserpin.","authors":"Carolin Hoefner, Ilaria Fregno, Maurizio Molinari","doi":"10.1080/27694127.2026.2712797","DOIUrl":"10.1080/27694127.2026.2712797","url":null,"abstract":"<p><p>Most proteins synthesized in the endoplasmic reticulum (ER) are covalently modified upon addition of pre-assembled oligosaccharides to side chains of asparagine (N) residues. Processing of <i>N</i>-linked oligosaccharides by ER-resident glucosidases, mannosidases and glucosyltransferases determines the fate of the associated polypeptides. Terminally glucose residues are removed from <i>N</i>-glycans to interrupt the engagement of ER-resident glucose-binding chaperones and promote secretion of native polypeptides. Mannose residues are removed to target terminally misfolded proteins for dislocation across the ER membrane and clearance by the cytoplasmic ubiquitin proteasome system (ER-associated degradation, ERAD). Recent evidence highlights the role of persistent <i>N</i>-glycan glucosylation as a signal that promotes ER lectins-driven segregation of misfolded proteins in ER subdomains that are eventually delivered to endolysosomal compartments for ER-to-Lysosome-Associated Degradation (ERLAD). Here we show that the polymerization-prone Portland variant of Neuroserpin (NS_PL) associated with familial encephalopathy with NS inclusion bodies (FENIB) is a client of the ERLAD machinery. Its lysosomal clearance relies on the LC3-dependent delivery branch of ERLAD involving the lectin chaperone Calnexin (CNX), the ERphagy receptor FAM134B and the SNARE protein Syntaxin17 (STX17), which is engaged upon persistent glucosylation of the NS_PL oligosaccharide linked at the asparagine residue at position 321.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2712797"},"PeriodicalIF":0.0,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698316","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}