3,906 results match your criteria Autophagy[Journal]


Distinct designer diamines promote mitophagy, and thereby enhance healthspan in and protect human cells against oxidative damage.

Autophagy 2022 May 17. Epub 2022 May 17.

Dept. Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem. PO Box 12271, Jerusalem, 9112102 Israel.

Impaired mitophagy is a primary pathogenic event underlying diverse aging-associated diseases such as Alzheimer and Parkinson diseases and sarcopenia. Therefore, augmentation of mitophagy, the process by which defective mitochondria are removed, then replaced by new ones, is an emerging strategy for preventing the evolvement of multiple morbidities in the elderly population. Based on the scaffold of spermidine (Spd), a known mitophagy-promoting agent, we designed and tested a family of structurally related compounds. Read More

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SQSTM1 and its MAP1LC3B-binding domain induce forced mitophagy to degrade mitochondrial carryover during mitochondrial replacement therapy.

Autophagy 2022 May 19:1-2. Epub 2022 May 19.

Fertility Preservation Lab, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, China.

Mitophagy is a process that selectively degrades mitochondria in cells, and it involves a series of signaling events. Our recent paper shows that the ectopic expression of SQSTM1 and its MAP1LC3B-binding domain (Binding) at the mitochondrial outer membrane, can directly cause mitophagy. To distinguish this mitophagy from others, we called it forced mitophagy. Read More

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Vacuole fragmentation depends on a novel Atg18-containing retromer-complex.

Autophagy 2022 May 15:1-18. Epub 2022 May 15.

Institute of Cellular Biochemistry, University Medicine, Goettingen, Germany.

The yeast PROPPIN Atg18 folds as a β-propeller with two binding sites for phosphatidylinositol-3-phosphate (PtdIns3P) and PtdIns(3,5)P at its circumference. Membrane insertion of an amphipathic loop of Atg18 leads to membrane tubulation and fission. Atg18 has known functions at the PAS during macroautophagy, but the functional relevance of its endosomal and vacuolar pool is not well understood. Read More

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N-methylguanosine (mG) tRNA modification: a novel autophagy modulator in cancer.

Autophagy 2022 May 16. Epub 2022 May 16.

Department of Otolaryngology, Center for Translational Medicine, Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Macroautophagy/autophagy, a physiological process that is involved in tumorigenesis, is regulated at genetic and epigenetic levels. Emerging reports suggest that aberrant RNA modifications cause dysregulated autophagy and affect tumorigenesis, while the role of RNA modifications in the regulation of autophagy in cancers remains unclear. In a recent study, we describe a new role for the tRNA mG methyltransferase complex components METTL1 and WDR4 as negative regulators of MTORC1-mediated autophagy in esophageal squamous cell carcinoma (ESCC). Read More

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Corrigendum.

Authors:

Autophagy 2022 May 13:1-2. Epub 2022 May 13.

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UXT attenuates the CGAS-STING1 signaling by targeting STING1 for autophagic degradation.

Autophagy 2022 May 11. Epub 2022 May 11.

State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, China.

STING1 (stimulator of interferon response cGAMP interactor 1), the pivotal adaptor protein of cGAS (cyclic GMP-AMP synthase)-STING1 signaling, is critical for type I IFN production of innate immunity. However, excessive or prolonged activation of STING1 is associated with autoinflammatory and autoimmune diseases. Thus, preventing STING1 from over-activation is important to maintain immune homeostasis. Read More

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LAMP2 regulates autophagy in the thymic epithelium and thymic stroma-dependent CD4 T cell development.

Autophagy 2022 May 19:1-14. Epub 2022 May 19.

Inovação em Saúde, Universidade do PortoInstituto de Investigação e , Porto, Portugal.

Within the thymus, thymic epithelial cells (TECs) provide dedicated thymic stroma microenvironments for T cell development. Because TEC functionality is sensitive to aging and cytoablative therapies, unraveling the molecular elements that coordinate their thymopoietic role has fundamental and clinical implications. Particularly, the selection of CD4 T cells depends on interactions between TCRs expressed on T cell precursors and self-peptides:MHC II complexes presented by cortical TECs (cTECs). Read More

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Hitchhiker's guide through the axon: transport and local translation of mRNA support axonal mitophagy.

Autophagy 2022 May 9:1-2. Epub 2022 May 9.

Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.

The unique cellular organization and metabolic demands of neurons pose a challenge in the maintenance of neuronal homeostasis. A critical element in maintaining neuronal health and homeostasis is mitochondrial quality control via replacement and rejuvenation at the axon. Dysregulation of mitochondrial quality control mechanisms such as mitophagy has been implicated in neurodegenerative diseases including Parkinson disease and amyotrophic lateral sclerosis. Read More

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Mitophagy: a new actor in the efficacy of chemo-immunotherapy.

Autophagy 2022 May 9:1-2. Epub 2022 May 9.

Cancer Biology Transfer Platform, Centre Georges-François Leclerc, Equipe Labellisée Ligue Contre le Cancer, Dijon, France.

Resistance to chemo-immunotherapy is a major issue for the treatment of non-small cell lung cancer. In a recent paper we unravel the role of MAPK in the capacity of restraining the therapeutic efficacy of chemo-immunotherapy. Inhibition of the MAPK pathway using a MAP2K/MEK inhibitor in combination with chemotherapy could promote OPTN (optineurin)-dependent mitophagy of cancer cells. Read More

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Actin assembly at sites of contact between the cortical ER and endocytic pits promotes ER autophagy.

Autophagy 2022 May 15:1-2. Epub 2022 May 15.

Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California, USA.

A recent screen of the deletion library implicated End3 in autophagy of the endoplasmic reticulum (ER). Together with Pan1, End3 coordinates endocytic site initiation with the localized assembly of branching actin filaments that promotes invagination of endocytic pits. Oxysterol binding proteins function as an inter-organelle bridge by interacting with VAP proteins on the cortical ER and type I myosins on the endocytic pit. Read More

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Proteotoxic stress disrupts epithelial integrity by inducing MTOR sequestration and autophagy overactivation.

Autophagy 2022 May 6:1-15. Epub 2022 May 6.

Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.

Macroautophagy/autophagy, an evolutionarily conserved degradation system, serves to clear intracellular components through the lysosomal pathway. Mounting evidence has revealed cytoprotective roles of autophagy; however, the intracellular causes of overactivated autophagy, which has cytotoxic effects, remain elusive. Here we show that sustained proteotoxic stress induced by loss of the NG and lch repeat-containing protein C53A5. Read More

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Nucleoporin POM121 signals TFEB-mediated autophagy via activation of SIGMAR1/sigma-1 receptor chaperone by pridopidine.

Autophagy 2022 May 4:1-26. Epub 2022 May 4.

Cellular Pathobiology Section, Integrative Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, DHHS, 333 Cassell Drive, Baltimore, Maryland 21224, USA.

Macroautophagy/autophagy is an essential process for cellular survival and is implicated in many diseases. A critical step in autophagy is the transport of the transcription factor TFEB from the cytosol into the nucleus, through the nuclear pore (NP) by KPNB1/importinβ1. In the C9orf72 subtype of amyotrophic lateral sclerosis-frontotemporal lobar degeneration (ALS-FTD), the hexanucleotide (G4C2)RNA expansion (HRE) disrupts the nucleocytoplasmic transport of TFEB, compromising autophagy. Read More

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Abnormal triaging of misfolded proteins by adult neuronal ceroid lipofuscinosis-associated DNAJC5/CSPα mutants causes lipofuscin accumulation.

Autophagy 2022 May 4:1-20. Epub 2022 May 4.

Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.

Mutations in are associated with adult neuronal ceroid lipofuscinosis (ANCL), a dominant-inherited neurodegenerative disease featuring lysosome-derived autofluorescent torage materials (AFSMs) termed lipofuscin. Functionally, DNAJC5 has been implicated in chaperoning synaptic proteins and in misfolding-associated protein secretion (MAPS), but how DNAJC5 dysfunction causes lipofuscinosis and neurodegeneration is unclear. Here we report two functionally distinct but coupled chaperoning activities of DNAJC5, which jointly regulate lysosomal homeostasis: While endolysosome-associated DNAJC5 promotes ESCRT-dependent microautophagy, a fraction of perinuclear and non-lysosomal DNAJC5 mediates MAPS. Read More

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SAMS-1 coordinates HLH-30/TFEB and PHA-4/FOXA activities through histone methylation to mediate dietary restriction-induced autophagy and longevity.

Autophagy 2022 May 3:1-17. Epub 2022 May 3.

Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Dietary restriction (DR) is known to promote autophagy to exert its longevity effect. While SAMS-1 (S-adenosyl methionine synthetase-1) has been shown to be a key mediator of the DR response, little is known about the roles of S-adenosyl methionine (SAM) and SAM-dependent methyltransferase in autophagy and DR-induced longevity. In this study, we show that DR and SAMS-1 repress the activity of SET-2, a histone H3K4 methyltransferase, by limiting the availability of SAM. Read More

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Targeting MCOLN1/TRPML1 channels to protect against ischemia-reperfusion injury by restoring the inhibited autophagic flux in cardiomyocytes.

Autophagy 2022 May 6:1-3. Epub 2022 May 6.

Jiangsu Province Key Laboratory of Anesthesiology Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu, China.

Accumulating evidence suggests that macroautophagy/autophagy dysfunction plays a critical role in myocardial ischemia-reperfusion (I/R) injury. However, the underlying mechanisms responsible for malfunctional autophagy in cardiomyocytes subjected to I/R are poorly understood. As a result, there are no effective therapeutic options that target autophagy to prevent myocardial I/R injury. Read More

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Tubular cells produce FGF2 via autophagy after acute kidney injury leading to fibroblast activation and renal fibrosis.

Autophagy 2022 May 18:1-22. Epub 2022 May 18.

Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA, USA.

Following acute kidney injury (AKI), renal tubular cells may stimulate fibroblasts in a paracrine fashion leading to interstitial fibrosis, but the paracrine factors and their regulation under this condition remain elusive. Here we identify a macroautophagy/autophagy-dependent FGF2 (fibroblast growth factor 2) production in tubular cells. Upon induction, FGF2 acts as a key paracrine factor to activate fibroblasts for renal fibrosis. Read More

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Mutations in V-ATPase in follicular lymphoma activate autophagic flux creating a targetable dependency.

Autophagy 2022 May 9:1-4. Epub 2022 May 9.

Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA.

The recent discovery of recurrent gene mutations in chaperones or components of the vacuolar-type H-translocating ATPase (V-ATPase) in follicular lymphoma (FL) was an unexpected finding. The application of whole exome sequencing and targeted gene re-sequencing has resulted in the identification of mutations in and in a combined 30% of FL, together constituting a major novel mutated pathway in this disease. Interestingly, no other human hematological malignancy carries these mutations at more than sporadic occurrences, implicating unique aspects of FL biology requiring these mutations. Read More

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Misfolded GBA/β-glucocerebrosidase impairs ER-quality control by chaperone-mediated autophagy in Parkinson disease.

Autophagy 2022 May 6:1-3. Epub 2022 May 6.

Department of Neurology, Columbia University, New York, NY, USA.

Inhibition of chaperone-mediated autophagy (CMA), a selective type of lysosomal degradation for intracellular proteins, may contribute to pathogenesis in neurodegenerative diseases including Parkinson disease (PD). Pathogenic variants of PD-related proteins that reside in the cytosol, including SNCA/alpha-synuclein, LRRK2 (leucine rich repeat kinase 2), UCHL1 (ubiquitin Cterminal hydrolase 1) and VPS35 (VPS35 retromer complex component), exert inhibitory effects on CMA. Decreased CMA activity has also been reported in sporadic PD patients, consistent with an association between CMA inhibition and PD. Read More

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Increased LCN2 (lipocalin 2) in the RPE decreases autophagy and activates inflammasome-ferroptosis processes in a mouse model of dry AMD.

Autophagy 2022 Apr 26:1-20. Epub 2022 Apr 26.

Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

In dry age-related macular degeneration (AMD), LCN2 (lipocalin 2) is upregulated. Whereas LCN2 has been implicated in AMD pathogenesis, the mechanism remains unknown. Here, we report that in retinal pigmented epithelial (RPE) cells, LCN2 regulates macroautophagy/autophagy, in addition to maintaining iron homeostasis. Read More

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Increased mitophagy protects cochlear hair cells from aminoglycoside-induced damage.

Autophagy 2022 Apr 26:1-17. Epub 2022 Apr 26.

State Key Laboratory of Bioelectronics, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, Jiangsu, China.

Aminoglycosides exhibit ototoxicity by damaging mitochondria, which in turn generate reactive oxygen species that induce hair cell death and subsequent hearing loss. It is well known that damaged mitochondria are degraded by mitophagy, an important mitochondrial quality control system that maintains mitochondrial homeostasis and ensures cell survival. However, it is unclear whether dysregulation of mitophagy contributes to aminoglycoside-induced hair cell injury. Read More

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Multifaceted roles of TAX1BP1 in autophagy.

Autophagy 2022 May 9:1-10. Epub 2022 May 9.

Department of Microbiology and Immunology, Penn State College School of Medicine, Hershey, Pennsylvania, USA.

TAX1BP1 is a selective macroautophagy/autophagy receptor that plays a central role in host defense to pathogens and in regulating the innate immune system. TAX1BP1 facilitates the xenophagic clearance of pathogenic bacteria such as and and regulates TLR3 (toll-like receptor 3)-TLR4 and DDX58/RIG-I-like receptor (RLR) signaling by targeting TICAM1 and MAVS for autophagic degradation respectively. In addition to these canonical autophagy receptor functions, TAX1BP1 can also exert multiple accessory functions that influence the biogenesis and maturation of autophagosomes. Read More

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Glutamine, MTOR and autophagy: a multiconnection relationship.

Autophagy 2022 Apr 26:1-2. Epub 2022 Apr 26.

Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Universidad Pablo de Olavide, Seville, Spain.

Cancer cells metabolize glutamine mostly through glutaminolysis, a metabolic pathway that activates MTORC1. The AMPK-MTORC1 signaling axis is a key regulator of cell growth and proliferation. Our recent investigation identified that the connection between glutamine and AMPK is not restricted to glutaminolysis. Read More

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Mitochondrial hitch-hiking of mRNA supports axonal mitophagy.

Autophagy 2022 May 3:1-2. Epub 2022 May 3.

F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA.

Mitostasis, the process of mitochondrial maintenance by biogenesis and degradative mechanisms, is challenged by the extreme length of axons. PINK1 (PTEN induced putative kinase 1) is a mitochondrial protein that targets damaged mitochondria for mitophagy. In reconciling the short half-life of PINK1 with the need for mitophagy of damaged axonal mitochondria, we found that axonal mitophagy depends on local translation of the mRNA. Read More

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Targeting impaired autophagy as a therapeutic strategy for Koolen-de Vries syndrome.

Autophagy 2022 Apr 29:1-3. Epub 2022 Apr 29.

Department of Cell Biology, State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, China Beijing, China.

Koolen-de Vries syndrome (KdVS) is a genomic disorder characterized by intellectual disability, heart failure, hypotonia and congenital malformations, which is caused by haploinsufficiency of . Because the pathogenesis of the disease is unknown, there is still no effective treatment. Here, we discuss our recent work identifying as an essential gene for macroautophagy/autophagy. Read More

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Atg39 binding to the inner nuclear membrane triggers nuclear envelope deformation in piecemeal macronucleophagy.

Autophagy 2022 Apr 29:1-2. Epub 2022 Apr 29.

School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan.

Recent studies have revealed that even the nucleus can be degraded by selective macroautophagy (hereafter macronucleophagy). In , the nuclear envelope (NE) protein Atg39 acts as a macronucleophagy receptor that mediates sequestration of nucleus-derived double-membrane vesicles (NDVs) into phagophores. The outer and inner membranes of these NDVs are derived from the outer and inner nuclear membranes (ONM and INM), respectively, and the lumen contains nucleoplasmic material. Read More

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Essential role of lysosomal Ca2+-mediated TFEB activation in mitophagy and functional adaptation of pancreatic β-cells to metabolic stress.

Autophagy 2022 May 1:1-3. Epub 2022 May 1.

Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.

Although the role of pancreatic β-cell macroautophagy/autophagy is well known, that of β-cell mitophagy is unclear. We investigated the changes of lysosomal Ca by mitochondrial or metabolic stress that can modulate TFEB activation and, additionally, the role of TFEB-induced mitophagy in β-cell function. Mitochondrial or metabolic stress induces mitophagy, which is mediated by lysosomal Ca release, increased cytosolic [Ca] and subsequent TFEB activation. Read More

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Intrinsic role of chaperone-mediated autophagy in cancer stem cell maintenance.

Autophagy 2022 Apr 27:1-2. Epub 2022 Apr 27.

Cellular Oncology Group, Biodonostia Health Research Institute, San Sebastian, Spain.

Chaperone-mediated autophagy (CMA) is a selective type of autophagy specialized in the individual degradation of targeted proteins. Its impact in any cancer stem cell (CSC) subtype remained elusive. In a recent study, we characterized the expression of LAMP2A and CMA activity in glioblastoma revealing its enrichment in a glioma stem cell (GSC) subpopulation. Read More

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Autophagy in age-related macular degeneration.

Autophagy 2022 May 1:1-13. Epub 2022 May 1.

University of Pittsburgh School of Medicine, Departments of Ophthalmology, Cell Biology, and Developmental Biology, Pittsburgh, PA, USA.

Age-related macular degeneration (AMD) is the leading cause of visual impairment in the aging population with limited understanding of its pathogenesis and a lack of effective treatment. The progression of AMD is initially characterized by atrophic alterations in the retinal pigment epithelium, as well as the formation of lysosomal lipofuscin and extracellular drusen deposits. Damage caused by chronic oxidative stress, protein aggregation and inflammatory processes may lead to geographic atrophy and/or choroidal neovascularization and fibrosis. Read More

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Hunting out the autophagic problem in Huntington disease.

Autophagy 2022 May 3:1-2. Epub 2022 May 3.

Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, Lund, Sweden.

Huntington disease is an inherited, progressive, incurable neurodegenerative disorder that primarily affects cells in the brain. Although the genetic basis for this condition has been known for nearly 30 years, how this causes disease is still unresolved. Of late there has been increasing evidence suggesting that dysfunction in macroautophagic/autophagic pathways may contribute to cellular dysfunction and death. Read More

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Chemotactic cell migration: the core autophagy protein ATG9A is at the leading edge.

Autophagy 2022 Apr 29:1-3. Epub 2022 Apr 29.

Cancer and Brain Genomics, Normandie University, UNIROUEN, INSERM U1245, Rouen, France.

Accumulating data indicate that several components of the macroautophagy/autophagy machinery mediate additional functions, which do not depend on autophagosome biogenesis or lysosomal cargo degradation. In this context, we found that the core autophagy protein ATG9A participates in the chemotactic movement of several cell lines, including highly invasive glioblastoma cells. Accordingly, ATG9A-depleted cells are unable to form large and persistent leading-edge protrusions. Read More

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