Autophagy reports最新文献

{"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":"https://doi.org/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}

{"title":"Kenny is the adaptor protein for ubiquitin-dependent mitophagy in <i>Drosophila melanogaster</i>.","authors":"Hubert Osei Acheampong, Ryan Insolera","doi":"10.1080/27694127.2026.2638025","DOIUrl":"10.1080/27694127.2026.2638025","url":null,"abstract":"<p><p>Mitophagy is the selective degradation program for damaged and unnecessary mitochondria to maintain cellular mitostasis and survival. Specific mutations in the mediators for the canonical ubiquitin (ub)-dependent mitophagy pathway have been identified with unique neurological diseases like Parkinson disease and ALS (amyotrophic lateral sclerosis), metabolic diseases, and cancer. Mammalian OPTN (optineurin) has been shown as a SAR (selective autophagy receptor) for ub-dependent mitophagy in vitro with direct connections of its mutations with glaucoma and ALS. Despite the in vitro demonstration of OPTN's role in mitophagy, the in vivo physiological characterization of OPTN's mitophagy function is largely unexplored. In our recent study, we provide in vivo evidence that the <i>Drosophila melanogaster</i> (Dm) protein, Kenny, directly mediates the sequestration of target mitochondria for the progression and completion of ub-dependent mitophagy. This result establishes Kenny as the Dm homolog of OPTN. Previously, Kenny had only been characterized for its role in innate immune activation and modulation. The conclusion from this study provides avenues for further understanding the in vivo signaling regulating Kenny's role in mitophagy and investigating homologous disease-relevant mutations of OPTN in Dm.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2638025"},"PeriodicalIF":0.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12962666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379835","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":"TMEM259/MEMBRALIN is a non-canonical ER-phagy receptor that associates with MAN1B1 and VCP to eliminate viral glycoproteins.","authors":"Jim Maurice Camilleri, Jing Zhang, Tao Wang, Iqbal Ahmad, Sunan Li, Yong-Hui Zheng","doi":"10.1080/27694127.2026.2639256","DOIUrl":"10.1080/27694127.2026.2639256","url":null,"abstract":"<p><p>Selective autophagy of the endoplasmic reticulum (ER-phagy/reticulophagy) is essential for organelle homeostasis and host defense, yet how ER quality control (ERQC) pathways distinguish viral glycoproteins from misfolded host proteins remains poorly understood. Recent work identifies TMEM259/MEMBRALIN (transmembrane protein 259) as a selective ER-phagy receptor containing a non-canonical LC3-interacting region (LIR) motif that assembles a dedicated ER-to-lysosome-associated degradation (ERLAD) complex targeting viral class I fusion glycoproteins. TMEM259 is a multi-pass ER membrane protein with luminal domains that recruit MAN1B1 (mannosyl-oligosaccharide 1,2-α-mannosidase) and cytosolic regions that engage VCP/p97 (valosin-containing protein). This TMEM259-MAN1B1-VCP axis directs diverse viral glycoproteins, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike, Ebola virus (EBOV) glycoprotein, influenza A virus (IAV) hemagglutinin (HA), and human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein, to lysosomes in a ubiquitin-independent manner. In contrast, misfolded host glycoproteins are primarily cleared through canonical ER-associated degradation (ERAD) or alternative ERLAD pathways. Preferential recognition of densely glycosylated viral substrates suggests that MAN1B1 may function as a glycan-density sensor, enabling TMEM259 to couple ER proteostasis with intrinsic antiviral immunity. These findings expand the conceptual framework of selective autophagy and uncover a specialized ER-phagy pathway dedicated to eliminating viral glycoproteins.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2639256"},"PeriodicalIF":0.0,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12962680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379846","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":"10.1080/27694127.2026.2637293","DOIUrl":"10.1080/27694127.2026.2637293","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1080/27694127.2024.2306766.].</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2637293"},"PeriodicalIF":0.0,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12962605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379851","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":"Mfi2: an outer mitochondrial membrane mitofissin required for mitophagy.","authors":"Kentaro Furukawa, Tatsuro Maruyama, Yuji Sakai, Nobuo N Noda, Tomotake Kanki","doi":"10.1080/27694127.2026.2635914","DOIUrl":"https://doi.org/10.1080/27694127.2026.2635914","url":null,"abstract":"<p><p>Mitophagy selectively eliminates damaged or excess mitochondria to maintain mitochondrial homeostasis. During this process, mitochondria need to be fragmented to allow their sequestration within autophagosomes. However, the well-known dynamin-related fission factors, Dnm1 in yeasts and DNM1L/DRP1 in mammals, are dispensable for mitophagy, leaving the underlying mechanism unresolved. In the yeast <i>Saccharomyces cerevisiae</i>, the identification of the mitochondrial intermembrane space protein Atg44 (autophagy-related 44) uncovered the existence of a new class of proteins, <i>mitofissin</i>, involved in mitochondrial fission during mitophagy. Whether Atg44 alone is sufficient for mitophagy-associated fission remained unclear. Our recent study identified Mfi2 (mitofissin 2) as a mitochondrial outer membrane-resident mitofissin that is required for efficient mitophagy and acts independently of Dnm1. Our findings indicate that mitophagy-associated mitochondrial fission is driven by mitofissins acting from both the inner and outer mitochondrial membranes. Here, we discuss remaining issues, including how mitofissin activities are regulated and how their function is modulated by mitochondrial lipids such as cardiolipin.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2635914"},"PeriodicalIF":0.0,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367316","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":"Microautophagy: current understanding of its molecular mechanisms and functions.","authors":"Yasuyoshi Sakai, Christian Behrends, Jayanta Debnath, Masanori Izumi, Andreas Jenny, Maurizio Molinari, Shuhei Nakamura, Masahide Oku, Marisa S Otegui, Laura Santambrogio, Han-Ming Shen, Tomohiko Taguchi, Michael Thumm, Takashi Ushimaru, Zhiping Xie, Ana Maria Cuervo, Fulvio Reggiori","doi":"10.1080/27694127.2026.2626661","DOIUrl":"10.1080/27694127.2026.2626661","url":null,"abstract":"<p><p>Microautophagy (MI-autophagy) is an umbrella term for intracellular degradative pathways that entail the invagination or protrusion of the limiting membranes of endolysosomal compartments, that is, late endosomes and mammalian lysosomes or yeast and plant vacuoles, followed by pinching-off of the membrane into the lumen of the organelle. During these processes, the material specifically and nonspecifically targeted for degradation is sequestered within the invaginating or protuberating membrane. In contrast to macroautophagy, the molecular mechanisms underlying MI-autophagy are largely unknown due to their diversity and complexity in location, regulation and molecular machinery requirements. Here, we review recent progress in the field of MI-autophagy, describing the molecular basis and functions of the MI-autophagic pathways reported to date in eukaryotic cells, from yeast to mammalian and plant cells.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2626661"},"PeriodicalIF":0.0,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12934144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147312655","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":"Mitofusin MFN2 acts as a molecular sensor preventing protein aggregation and mitophagy, with a protective effect against apoptosis in Charcot-Marie-Tooth type 2A disease.","authors":"Mariana Joaquim, Maike F Dohrn, Arnaud Chevrollier, Mafalda Escobar-Henriques","doi":"10.1080/27694127.2026.2629624","DOIUrl":"https://doi.org/10.1080/27694127.2026.2629624","url":null,"abstract":"<p><p>Mitochondria are central hubs for cellular fitness, empowered by plastic remodeling of their shape, proteome composition, and/or metabolic state. MFN2 (mitofusin 2) mediates mitochondrial fusion and ensures adaptations in response to metabolic changes and stresses. Besides this canonical role, MFN2 serves as a communication hub with other organelles. It tethers mitochondria to the endoplasmic reticulum (ER), lipid droplets, and peroxisomes, regulating calcium buffering, apoptosis, lipid biosynthesis, and lipolysis. Dysfunctional MFN2 causes the hereditary neuropathy Charcot-Marie-Tooth type 2A (CMT2A) and is linked to several metabolic diseases. In a recent publication, we described another fusion-independent role of MFN2 in proteostasis and mitophagy. MFN2 binds the chaperone HSPA8/HSC70 (heat shock protein family A [Hsp70] member 8) and the proteasome, a key function in maintaining mitochondrial and cellular protein quality control, which appears to be lost in the context of CMT2A-associated <i>MFN2</i> variants.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2629624"},"PeriodicalIF":0.0,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12928653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286400","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 New biosensor illuminates the driving force behind mitochondrial outer membrane rupture.","authors":"Wei-Hua Chu, Wei-Chung Chiang","doi":"10.1080/27694127.2026.2627062","DOIUrl":"https://doi.org/10.1080/27694127.2026.2627062","url":null,"abstract":"<p><p>In PINK1 (PTEN induced kinase 1)/PRKN (Parkin)-mediated mitophagy, the rupture of the outer mitochondrial membrane (OMM) emerges as a crucial event required for efficient mitochondrial clearance. Mechanistically, OMM rupture exposes inner mitochondrial membrane (IMM) mitophagy receptors, facilitating subsequent autophagic removal. Despite the important role of OMM rupture in mitophagy, the underlying mechanism remains elusive and technically difficult to monitor. In a recent study, we developed a novel fluorescent biosensor to directly visualize OMM rupture. This technique enables temporal and spatial characterization of OMM rupture and provides a powerful platform to dissect the underlying mechanism. Using this tool, we revealed that VCP (valosin containing protein) and its recruitment factors are required for OMM rupture, suggesting that VCP-dependent remodeling of the OMM proteome primes the rupture of OMM during mitophagy. <b>Abbreviations</b>: ARIH1, Ariadne RBR E3 ubiquitin protein Ligase 1; AMFR, autocrine motility factor receptor; ANKRD13A, ankyrin repeat domain-containing protein 13 A; FUNDC1, FUN14 domain containing 1; OA, oligomycin and antimycin; CID, chemical-induced dimerization; IMM, nner mitochondrial membrane; LC3, microtubule-associated protein 1 light chain 3; MUL1, mitochondrial E3 ubiquitin protein ligase 1; NIX, BCL2 interacting protein 3 like; OMM, outer mitochondrial membrane; UBXN1, ubiquitin regulatory X domain-containing protein 1; UBXN6, ubiquitin regulatory X domain-containing protein 6; VCP, valosin-containing protein; WIPI2, WD repeat domain phosphoinositide interacting protein 2.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2627062"},"PeriodicalIF":0.0,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146229865","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":"TFEB confers resistance against the chemotherapeutic agent CX-5461.","authors":"Marjorie Rolland, Benoît Marchand, Laure Bessy, Florence McDuff, Marie-Josée Boucher","doi":"10.1080/27694127.2026.2624259","DOIUrl":"https://doi.org/10.1080/27694127.2026.2624259","url":null,"abstract":"<p><p>Identifying mechanisms underlying chemoresistance is essential for improving the efficacy of chemotherapeutic drugs. Previously, we showed that cancer cells respond to gemcitabine by activating protective signals dependent on the master regulator of autophagy and lysosomal biogenesis, transcription factor EB (TFEB). However, how gemcitabine triggers these protective responses remains elusive. While gemcitabine primarily aims at disrupting DNA replication, it is also suspected to induce nucleolar stress. In this study, we aimed to examine the effect of gemcitabine on nucleolar stress and investigate whether nucleolar stress inducers could trigger TFEB-dependent protective signals. Besides gemcitabine causing nucleolar stress, the anticancer agent CX-5461, primarily designed to induce nucleolar stress, promoted TFEB nuclear accumulation. Interfering with TFEB improved the sensitivity of cancer cells to both CX-5461 and gemcitabine. Our findings suggest that TFEB provides broad protection against the stress caused by chemotherapeutic drugs, representing a promising target for intercepting chemoresistance and improving the efficacy of anticancer agents.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2624259"},"PeriodicalIF":0.0,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146229885","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 kidney physiology: from cellular quality control to organ metabolism.","authors":"Takeshi Yamamoto, Satoshi Minami, Yoshitaka Isaka","doi":"10.1080/27694127.2026.2622228","DOIUrl":"10.1080/27694127.2026.2622228","url":null,"abstract":"<p><p>Autophagy is a cellular process that maintains kidney physiology by recycling intracellular components to preserve homeostasis. In the kidney, autophagy supports energy metabolism and integrity across multiple cell types. Its regulation is tightly governed by nutrient availability, hormonal cues, and oxygen levels, primarily through signaling pathways such as mechanistic target of rapamycin kinase (mTOR), AMP-activated protein kinase (AMPK), and transcription factor EB (TFEB). Under physiological conditions, autophagy is dynamically regulated to meet metabolic demands. However, aging, obesity, and metabolic stress impair lysosomal function, leading to a pathological state termed autophagic stagnation, in which autophagosomes accumulate but degradative flux is compromised. Rather than being uniformly protective, this stagnation promotes cellular damage and contributes to kidney disease progression. Notably, autophagic stagnation in proximal tubular epithelial cells (PTECs) contributes to acute kidney injury (AKI)-to-chronic kidney disease (CKD) transition and exacerbates lipotoxicity in obesity-related kidney disease. Recent studies highlight the importance of transcriptional regulators - including TFEB and MondoA - in maintaining autophagic activity and mitochondrial homeostasis. Therapeutic strategies aimed at restoring autophagic flux - pharmacologically or through lifestyle interventions such as caloric restriction - hold promise for preserving kidney function. Deeper understanding of cell type - specific autophagy regulation will be critical for developing targeted and context-specific therapies.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"5 1","pages":"2622228"},"PeriodicalIF":0.0,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146159448","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}