Autophagy reports最新文献

{"title":"Retinal ganglion cell autophagy: a housekeeper essential for neuronal homeostasis and survival.","authors":"Yogapriya Sundaresan, Gulab S Zode","doi":"10.1080/27694127.2026.2710457","DOIUrl":"10.1080/27694127.2026.2710457","url":null,"abstract":"<p><p>Retinal ganglion cells (RGCs) are the sole projection neurons of the retina and the only direct link between retinal circuitry and the brain. Maintaining this lifelong connection requires constitutive autophagy to preserve organelle quality control and neuronal homeostasis. Although autophagy has been widely studied following ocular hypertension and optic nerve injury, its physiological role in healthy RGCs has remained unclear. We have recently revealed that basal autophagy is highly active in RGCs and that conditional deletion of <i>Atg5</i> or <i>Atg7</i> is sufficient to induce progressive RGC dysfunction, optic nerve degeneration, and neurodegeneration. Autophagy deficiency caused the accumulation of swollen mitochondria, distended endoplasmic reticulum, fragmented Golgi, synaptic vesicles, and incomplete autophagosomes accompanied by increased p62 and LC3B levels. These findings establish basal autophagy as an essential housekeeping mechanism that preserves organelle quality control and long-term RGC integrity.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2710457"},"PeriodicalIF":0.0,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698306","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":"FLCN loss is characterized by SQSTM1/p62 accumulation despite functional autophagy flux in Birt-Hogg-Dubé syndrome-associated kidney cancer.","authors":"Halvor Ullern, Julie Aarmo Johannessen, Feyza Kasikci, Miriam Formica, Naghmeh Karimi Melve, Siri Andresen, Andreas Brech, Karol Axcrona, Kjersti Jørgensen, Lorant Farkas, Jorrit M Enserink, Helene Knævelsrud","doi":"10.1080/27694127.2026.2705631","DOIUrl":"10.1080/27694127.2026.2705631","url":null,"abstract":"<p><p>Birt-Hogg-Dubé syndrome (BHD) is an autosomal, dominant condition caused by <i>Folliculin</i> (FLCN) mutation and characterized by enhanced risk for kidney tumors. Previous studies have shown constitutive nuclear localization of the transcription factor TFEB and simultaneous hyperactivation of canonical MTORC1 signaling in the absence of FLCN. Here we assess the impact on autophagy under the situation of combined anabolic and catabolic activation. Using an established BHD patient-derived kidney cancer cell line, we confirmed that TFEB was permanently localized in the nucleus combined with an increase in canonical MTORC1 signaling, whereas bulk autophagy flux and LC3 lipidation were unaffected by <i>FLCN</i> status. However, we found that the autophagy receptor SQSTM1/p62 accumulated in enlarged puncta in the absence of FLCN. Finally, we recapitulate aberrant p62 accumulation in a Norwegian cohort of BHD kidney tumor samples. Our results demonstrate that FLCN loss is characterized by SQSTM1/p62 accumulation, although SQSTM1/p62 appears dispensable for anchorage-independent growth in cell models.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2705631"},"PeriodicalIF":0.0,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698327","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":"Damage control: new functions for the Arp2/3 complex and WHAMM in autophagy and lysosomal homeostasis.","authors":"Lianna H Wagner, Kenneth G Campellone","doi":"10.1080/27694127.2026.2698348","DOIUrl":"10.1080/27694127.2026.2698348","url":null,"abstract":"<p><p>Macroautophagy is an intracellular degradation process that relies on autophagosomes and lysosomes to maintain cellular and organismal homeostasis. Actin cytoskeletal rearrangements driven by the Arp2/3 (actin-related protein 2/3) complex, an essential actin nucleator, impact multiple steps of this pathway, but where and when Arp2/3-mediated actin assembly is most influential has remained unclear. Recent work now shows that the Arp2/3 complex is crucial in the later stages of autophagy due to its function in maintaining lysosomal integrity. WHAMM (WASP homolog associated with actin, membranes, and microtubules) is the key nucleation-promoting factor that activates Arp2/3 at permeabilized lysosomes, uncovering new roles for actin, the Arp2/3 complex, and WHAMM in lysosomal damage responses.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2698348"},"PeriodicalIF":0.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13360509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148439115","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 in the liver.","authors":"Elijah Burks, Jenna Copes, Kelly Nguyen, Albert Tawil-Brown, Shengmin Yan","doi":"10.1080/27694127.2026.2698350","DOIUrl":"10.1080/27694127.2026.2698350","url":null,"abstract":"<p><p>The liver plays a dynamic role in maintaining whole-body homeostasis through its control of nutrient metabolism, detoxification, and immune regulation. Autophagy, a conserved lysosomal degradation pathway, is central to these functions, enabling hepatocytes to adapt to fluctuations in nutrient availability, hormonal signals, and cellular stress. Hepatic autophagy is tightly regulated by nutrient and energy-sensing pathways, including AMPK, mTOR, the coordinated actions of insulin and glucagon, and transcriptional regulators TFEB, FOXO proteins, PPAR isoforms, FXR, and NRF2. Epigenomic mechanisms, chromatin remodeling complexes, and post-transcriptional regulators, such as microRNAs (miRNAs), RNA-binding proteins (RBPs), and liquid-liquid phase separation (LLPS), further refine autophagy gene expression and autophagosome formation. In physiological conditions, autophagy maintains hepatocyte integrity by supporting lipid, carbohydrate, and protein turnover and by clearing damaged or excess organelles through selective pathways such as mitophagy, lipophagy, pexophagy, ER-phagy, and xenophagy. Autophagy dysfunction contributes to the development of various liver diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), cholestatic liver disease, liver fibrosis, and hepatocellular carcinoma (HCC). Understanding the diverse regulatory networks governing hepatic autophagy, along with the roles of autophagy in liver homeostasis, provides new opportunities for therapeutic intervention. This review summarizes existing findings on the role of autophagy in the liver, focusing on recent advances in the regulation of hepatic autophagy. It also highlights unresolved mechanisms and discusses how targeting autophagy may offer novel strategies for treating liver diseases.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2698350"},"PeriodicalIF":0.0,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13348988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148426906","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":"Glucose concentration of neuronal media formulations influences PINK1-dependent mitophagy in human iNeurons.","authors":"Benjamin O'Callaghan, Daniela Melandri, Darija Soltic, Katharina Cosker, Marc P M Soutar, James R Evans, Hannah Lucas-Clarke, Joe Robin, Sonia Gandhi, Nicol Birsa, Charles Arber, Selina Wray, Helene Plun-Favreau","doi":"10.1080/27694127.2026.2685472","DOIUrl":"10.1080/27694127.2026.2685472","url":null,"abstract":"<p><p>Parkinson's disease-associated proteins PINK1 and Parkin collaboratively regulate stress-induced mitophagy. While <i>in vitro</i> human neuronal cultures are valuable for studying the roles of PINK1 and Parkin in a disease-relevant context, the impact of culture conditions on these processes remains largely underexplored. Here, it is shown that human induced neurons (iNeurons) cultured in N2B27 and BrainPhys medium exhibit distinct PINK1-Parkin-dependent mitophagy phenotypes. Specifically, BrainPhys-cultured iNeurons show greater resistance to PINK1-dependent mitophagy initiation, linked to a reduction in glucose availability and reduced PINK1 protein availabilities, leading to decreases in stress-induced and basal mitophagy fluxes. These findings highlight the critical impact of culture conditions on mitophagy dynamics and emphasize the need to account for media-specific differences when using <i>in vitro</i> models to investigate mitophagy mechanisms in human neurons.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2685472"},"PeriodicalIF":0.0,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13274156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148280084","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":"Seeing is believing: visualizing spatiotemporal lipophagic flux in vivo with the tfLiveDrop reporter mice.","authors":"Siqiao Gong, Chen Yang, Huafeng Liu","doi":"10.1080/27694127.2026.2687045","DOIUrl":"10.1080/27694127.2026.2687045","url":null,"abstract":"<p><p>Lipophagy, the selective autophagic degradation of lipid droplets (LDs), is central to cellular lipid homeostasis, yet its dynamic regulation in living organisms has remained largely unobservable in real time. To overcome this barrier, we recently developed the mCherry‑eGFP‑LiveDrop (tfLiveDrop) reporter mice, in which a pH‑sensitive tandem fluorescent probe targeted to LDs via the GPAT4‑derived LiveDrop domain enables real‑time, single‑cell visualization of lipophagic flux in vivo. Using tfLiveDrop mice, we uncovered pronounced organ heterogeneity in basal lipophagy, identified an organ‑specific lipophagic inhibition in type 2 diabetes, and revealed a previously unrecognized developmentally programmed lipophagy induction that drives renal metabolic maturation. Together, these findings demonstrate that tfLiveDrop is a sensitive and versatile reporter for in vivo lipophagy research.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2687045"},"PeriodicalIF":0.0,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13274137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148280103","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":"AMPK-mediated autophagy induction by bisdemethoxycurcumin attenuates senescence and amyloid pathology in 3xTg-AD mice.","authors":"Parul Khajuria, Dilpreet Kour, Kuhu Sharma, Lakhvinder Singh, Razia Banoo, Diksha Manhas, P Ramajayan, Utpal Nandi, Sandip B Bharate, Zabeer Ahmed, Ajay Kumar","doi":"10.1080/27694127.2026.2675164","DOIUrl":"10.1080/27694127.2026.2675164","url":null,"abstract":"<p><p>Alzheimer disease (AD) pathology is accompanied by increased senescence and reduced levels of autophagy in the brain. We investigated whether pharmacologically inducing autophagy could alter the senescent phenotype and ameliorate AD pathology. We discovered that Bisdemethoxycurcumin (BDMC), a natural compound found in <i>Curcuma longa</i>, stimulates autophagy in primary astrocytes. We found that autophagy and senescence exhibit an inverse relationship in aging astrocytes, with increased expression of senescent proteins and downregulation of autophagic proteins. However, treatment of aged astrocytes with BDMC reversed the senescent phenotype by ameliorating the impaired autophagy. Interestingly, the senescent phenotype persisted when autophagy was downregulated by knockdown of <i>AMPK</i>. Additionally, BDMC-induced autophagy aided in the removal of amyloid beta (Aβ) that was administered externally to the astrocytes. Further, to validate these results in a mouse model of AD, we confirmed that BDMC significantly penetrates the blood-brain barrier (BBB) in mice. Therefore, we administered 50 and 100 mg/kg b.w. of BDMC to transgenic 3xTg-AD mice for two months. In their hippocampus, the Control 3xTg-AD animals showed more senescent cells and lower autophagy levels. In contrast, autophagic proteins were significantly upregulated while senescence indicators, such as senescence-associated secretory phenotype (SASP) proteins, were sharply downregulated in the brain of treated animals. We discovered that the hippocampus of treated mice had a significantly lower Aβ load. These molecular changes in the brain were ultimately reflected in the improved working memory and neuromuscular coordination behavior of mice treated with BDMC. This study warrants further evaluation of BDMC for the management of AD.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2675164"},"PeriodicalIF":0.0,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13245070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148213657","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":"Beyond cargo clearance: p62 coordinates cAMP signalling and autophagy to drive cell fate decisions in <i>Dictyostelium discoideum</i>.","authors":"Saksham Gautam, Shweta Saran","doi":"10.1080/27694127.2026.2674406","DOIUrl":"10.1080/27694127.2026.2674406","url":null,"abstract":"<p><p>p62 is a multi-domain selective autophagy receptor and signaling scaffold conserved across eukaryotes. However, its evolutionary roots and functional significance in early-diverging eukaryotes like <i>Dictyostelium</i> have remained unexplored. In our recent study, we characterized p62 in the social amoeba <i>Dictyostelium discoideum</i>. Loss of <i>p62</i> significantly delayed the starvation induced development and led to the formation of smaller multicellular structures. Altered p62 levels also disrupted autophagy flux and cell fate commitment in <i>Dictyostelium</i> cells. Treatment of <i>p62</i> knockout (<i>p62^-</i> ) cells with pulses of exogenous cyclic AMP (cAMP) partially rescued developmental defects, suggesting a potential role for p62 in sustaining intracellular cAMP levels necessary for development. Taken together, p62 emerges as an evolutionarily conserved coordinator of nutrient sensing, second messenger signaling, and autophagy that promotes multicellular development in <i>Dictyostelium</i>.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2674406"},"PeriodicalIF":0.0,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13192089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148018973","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 review of autophagy in the pancreas: normal physiology and pathophysiology.","authors":"Miles Piper, Conan Kinsey","doi":"10.1080/27694127.2026.2665907","DOIUrl":"10.1080/27694127.2026.2665907","url":null,"abstract":"<p><p>Autophagy is a complex cellular process of cellular degradation that is essential for healthy pancreatic function and, when perturbed, can result in pathological states such as pancreatitis, diabetes, and cancer. Extremes in both activation and inhibition can lead to inflammation, cell damage, and organ dysfunction. Pharmacologic targeting of autophagy to restore homeostasis may provide a therapeutic benefit to various pancreatic pathological processes. In this review, we discuss the current understanding of how autophagy maintains normal pancreatic function and is perturbed in various pancreatic disease states, including opportunities for potential therapeutic intervention.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2665907"},"PeriodicalIF":0.0,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13170389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147943919","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 selectively clears ER in TNF-α-induced muscle atrophy.","authors":"Ursula K Dueren, Alan An Jung Wei, A Elisabeth Gressler, Simon Rapp, Oliver Popp, Robert Kerridge, Viviana Buonomo, Paolo Grumati, Philipp Mertins, Matthias Selbach, Anna Katharina Simon, Thomas Sommer","doi":"10.1080/27694127.2026.2649064","DOIUrl":"10.1080/27694127.2026.2649064","url":null,"abstract":"<p><p>Skeletal muscle atrophy is a pathological condition characterized by the progressive loss of muscle mass and function, driven by factors such as disuse, inflammation, and aging. While the ubiquitin-proteasome system is established as the central mediator of myofibrillar protein degradation, the role of selective autophagy and the degradation of organelles remains underexplored in this context. To address this, we employed a quantitative, time-resolved <i>in vitro</i> analysis of protein synthesis and degradation in C2C12 myotubes undergoing TNF-α-induced atrophy, using dynamic Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) coupled with LC-MS/MS. Our data challenges the classical view of atrophy as a uniform, degradation-centric process. Instead, we reveal temporally distinct patterns of selective protein turnover, including differential degradation of myofibrillar, ribosomal, and endoplasmic reticulum (ER)-resident proteins. Early atrophy is characterized by suppressed short-term protein synthesis, increased ubiquitin-ligase expression, proteasomal activation, and ribosome turnover. In contrast, late atrophy features proteasome-dependent myofibrillar protein degradation, selective synthesis, and degradation of mitochondrial and cytoplasmic ribosomes, indicative of metabolic adaptation. Moreover, we identify a temporal shift in autophagic selectivity: from ER homeostasis to a stress-induced ER-degradation program. Notably, autophagy inhibition during atrophy leads to the accumulation of ER-phagy receptors Tex264 and Calcoco1, implicating ER-phagy as a key contributor to atrophic remodeling and highlighting receptor-mediated selective autophagy as a regulatory axis in muscle proteostasis. By elucidating the role of ER-phagy, this study opens avenues for therapeutic interventions targeting proteostasis in inflammation-induced muscle-wasting, contributing to a refined understanding of muscle atrophy beyond proteasomal degradation, particularly in acute inflammatory conditions such as sepsis.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2649064"},"PeriodicalIF":0.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13081748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147700837","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}