3,593 results match your criteria Autophagy[Journal]

Autophagy is critical for cysteine metabolism in pancreatic cancer through regulation of SLC7A11.

Autophagy 2021 May 14:1-2. Epub 2021 May 14.

Department of Radiation Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY, USA.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer. The elevated macroautophagy/autophagy in these tumors supports growth, promotes immune evasion, and increases therapeutic resistance. Therefore, targeting autophagy is a therapeutic strategy that is being pursued to treat PDAC patients. Read More

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Deletion of inhibits neointima formation by enhancing KAT2A/GCN5-mediated acetylation of TUBA/α-tubulin .

Autophagy 2021 May 14:1-18. Epub 2021 May 14.

Center of Molecular and Translational Medicine, Georgia State University, Atlanta, Georgia.

ULK1 (unc-51 like autophagy activating kinase) has a central role in initiating macroautophagy/autophagy, a process that contributes to atherosclerosis and neointima hyperplasia, or excessive tissue growth that leads to vessel dysfunction. However, the role of ULK1 in neointima formation remains unclear. We aimed to determine how deletion affected neointima formation and to investigate the underlying mechanisms. Read More

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V-ATPase controls tumor growth and autophagy in a Drosophila model of gliomagenesis.

Autophagy 2021 May 12:1-11. Epub 2021 May 12.

Department of Biosciences, Università Degli Studi Di Milano, Milan, Italy.

Glioblastoma (GBM), a very aggressive and incurable tumor, often results from constitutive activation of EGFR (epidermal growth factor receptor) and of phosphoinositide 3-kinase (PI3K). To understand the role of autophagy in the pathogenesis of glial tumors , we used an established model of glioma based on overexpression in larval glial cells of an active human and of the PI3K homolog . Interestingly, the resulting hyperplastic glia express high levels of key components of the lysosomal-autophagic compartment, including vacuolar-type H-ATPase (V-ATPase) subunits and ref(2)P (refractory to Sigma P), the homolog of SQSTM1/p62. Read More

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CUL3 (cullin 3)-mediated ubiquitination and degradation of BECN1 (beclin 1) inhibit autophagy and promote tumor progression.

Autophagy 2021 May 12:1-18. Epub 2021 May 12.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.

Macroautophagy/autophagy plays an important role during the development of human cancer. BECN1 (beclin 1), a core player in autophagy regulation, is downregulated in many kinds of malignancy. The underlying mechanism, however, has not been fully illuminated. Read More

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PRKA/PKA signals and autophagy: space matters.

Autophagy 2021 May 10:1-2. Epub 2021 May 10.

Department of Molecular Medicine, University of Pavia, Pavia, Italy.

Macroautophagy/autophagy is the cellular process responsible for the elimination and recycling of aggregated proteins and damaged organelles. Whereas autophagy is strictly regulated by several signaling cascades, the link between this process and the subcellular distribution of its regulatory pathways remains to be established. Our recent work suggests that the compartmentalization of PRKA/PKA (protein kinase cAMP-activated) determines its effects on autophagy. Read More

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Phosphoregulation of the autophagy machinery by kinases and phosphatases.

Autophagy 2021 May 10:1-20. Epub 2021 May 10.

Department of Cell Biology, University of Groningen, University Medical Center Groningen, AV Groningen, The Netherlands.

Eukaryotic cells use post-translational modifications to diversify and dynamically coordinate the function and properties of protein networks within various cellular processes. For example, the process of autophagy strongly depends on the balanced action of kinases and phosphatases. Highly conserved from the budding yeast to humans, autophagy is a tightly regulated self-degradation process that is crucial for survival, stress adaptation, maintenance of cellular and organismal homeostasis, and cell differentiation and development. Read More

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A protective variant of the autophagy receptor CALCOCO2/NDP52 in Multiple Sclerosis (MS).

Autophagy 2021 May 10:1-3. Epub 2021 May 10.

IRCCS Fondazione Santa Lucia, Rome, Italy.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, which has been found associated with dysfunctional mitochondria. In order to advance our understanding of the complex molecular mechanisms underlying this disease, we analyzed mitophagy, a process fundamental for the elimination of damaged mitochondria through the autophagic process, in peripheral blood mononuclear cells (PBMCs) of MS patients. Through a genetic analysis carried out on 203 MS patients and 1000 healthy controls, we identified a natural variant of CALCOCO2/NDP52, a well-known autophagic receptor, associated with and protective in MS. Read More

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Chaperone-mediated autophagy controls the turnover of E3 ubiquitin ligase MARCHF5 and regulates mitochondrial dynamics.

Autophagy 2020 Dec 1:1-16. Epub 2020 Dec 1.

Department of Neurology, First Affiliated Hospital of GuangZhou Medical University, Guangzhou, Guangdong, China.

As a highly dynamic organelle, mitochondria undergo constant fission and fusion to change their morphology and function, coping with various stress conditions. Loss of the balance between fission and fusion leads to impaired mitochondria function, which plays a critical role in the pathogenesis of Parkinson disease (PD). Yet the mechanisms behind mitochondria dynamics regulation remain to be fully illustrated. Read More

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December 2020

Lipotoxicity reduces DDX58/Rig-1 expression and activity leading to impaired autophagy and cell death.

Autophagy 2021 May 9:1-19. Epub 2021 May 9.

Institute of Metabolic Disorders, Genesis Biotechnology Group, Hamilton, NJ, USA.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally. NAFLD is a consequence of fat accumulation in the liver leading to lipotoxicity. Increasing evidence has demonstrated the critical role of autophagy in NAFLD. Read More

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VCP/p97 cofactor UBXN1/SAKS1 regulates mitophagy by modulating MFN2 removal from mitochondria.

Autophagy 2021 May 9:1-20. Epub 2021 May 9.

Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.

Initiation of PINK1- and PRKN-dependent mitophagy is a highly regulated process involving the activity of the AAA-ATPase VCP/p97, a cofactor-guided multifunctional protein central to handling ubiquitinated client proteins. Removal of ubiquitinated substrates such as the mitofusin MFN2 from the outer mitochondrial membrane by VCP is critical for PRKN accumulation on mitochondria, which drives mitophagy. Here we characterize the role of the UBA and UBX-domain containing VCP cofactor UBXN1/SAKS1 during mitophagy. Read More

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CREG1 promotes lysosomal biogenesis and function.

Autophagy 2021 May 8:1-17. Epub 2021 May 8.

Department of Surgery, Rutgers University-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

CREG1 is a small glycoprotein which has been proposed as a transcription repressor, a secretory ligand, a lysosomal, or a mitochondrial protein. This is largely because of lack of antibodies for immunolocalization validated through gain- and loss-of-function studies. In the present study, we demonstrate, using antibodies validated for immunofluorescence microscopy, that CREG1 is mainly localized to the endosomal-lysosomal compartment. Read More

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Dendritic cell PIK3C3/VPS34 controls the pathogenicity of CNS autoimmunity independently of LC3-associated phagocytosis.

Autophagy 2021 May 7:1-10. Epub 2021 May 7.

Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.

PIK3C3/VPS34 is a key player in macroautophagy/autophagy and MAP1LC3/LC3-associated phagocytosis (LAP), which play critical roles in dendritic cell (DC) function. In this study, we assessed the contribution of PIK3C3 to DC function during experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). We found that -deficient DCs exhibit attenuated capacity to reactivate encephalitogenic T cells in the central nervous system, leading to reduced incidence and severity of EAE in DC-specific -deficient mice. Read More

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ATG4D role in mAtg8s delipidation and neuroprotection.

Autophagy 2021 May 7:1-3. Epub 2021 May 7.

Departamento de Biología Funcional, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain.

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The human vault RNA enhances tumorigenesis and chemoresistance through the lysosome in hepatocellular carcinoma.

Autophagy 2021 May 7:1-13. Epub 2021 May 7.

Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland.

The small non-coding (vault RNA 1-1) is known to confer resistance to apoptosis in several malignant cell lines and to also modulate the macroautophagic/autophagic flux in hepatocytes, thus highlighting its pro-survival role. Here we describe a new function of in regulating and tumor cell proliferation, tumorigenesis and chemoresistance. Knockout (KO) of in human hepatocellular carcinoma cells reduced nuclear localization of TFEB (transcription factor EB), leading to a downregulation of the coordinated lysosomal expression and regulation (CLEAR) network genes and lysosomal compartment dysfunction. Read More

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Upregulation of brain cholesterol levels inhibits mitophagy in Alzheimer disease.

Autophagy 2021 May 4:1-3. Epub 2021 May 4.

Department of Cell Death and Proliferation, Institut d'Investigacions Biomèdiques de Barcelona (IIBB-CSIC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Mitochondrial dysfunction is behind several neurodegenerative diseases, including Alzheimer disease (AD). Accumulation of damaged mitochondria is already observed at the early stages of AD and has been linked to impaired mitophagy, but the mechanisms underlying this alteration are still not fully known. In our recent study, we show that intracellular cholesterol enrichment can downregulate amyloid beta (Aβ)-induced mitophagy. Read More

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How autophagy controls the intestinal epithelial barrier.

Autophagy 2021 Apr 27:1-18. Epub 2021 Apr 27.

Department of Immunology, University of Toronto, Toronto, Canada.

Macroautophagy/autophagy is a cellular catabolic process that results in lysosome-mediated recycling of organelles and protein aggregates, as well as the destruction of intracellular pathogens. Its role in the maintenance of the intestinal epithelium is of particular interest, as several autophagy-related genes have been associated with intestinal disease. Autophagy and its regulatory mechanisms are involved in both homeostasis and repair of the intestine, supporting intestinal barrier function in response to cellular stress through tight junction regulation and protection from cell death. Read More

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The influence of circular RNAs on autophagy and disease progression.

Autophagy 2021 Apr 27:1-14. Epub 2021 Apr 27.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

Circular RNAs (circRNAs) are non-coding RNAs that have attracted considerable attention in recent years. Owing to their distinct circular structure, circRNAs are stable in cells. Autophagy is a catabolic process that helps in the degradation and recycling of harmful or inessential biological macromolecules in cells and enables cells to adapt to stress and changes in the internal and external environments. Read More

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MCOLN1/TRPML1 finely controls oncogenic autophagy in cancer by mediating zinc influx.

Autophagy 2021 Apr 23:1-22. Epub 2021 Apr 23.

Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China.

Macroautophagy/autophagy is elevated to ensure the high demand for nutrients for the growth of cancer cells. Here we demonstrated that MCOLN1/TRPML1 is a pharmaceutical target of oncogenic autophagy in cancers such as pancreatic cancer, breast cancer, gastric cancer, malignant melanoma, and glioma. First, we showed that activating MCOLN1, by increasing expression of the channel or using the MCOLN1 agonists, ML-SA5 or MK6-83, arrests autophagic flux by perturbing fusion between autophagosomes and lysosomes. Read More

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Comment on "mt-Keima detects PINK1-PRKN mitophagy with greater sensitivity than mito-QC".

Autophagy 2021 Apr 23:1-2. Epub 2021 Apr 23.

Inherited Movement Disorders Unit, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

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HIV-1 Vpr protein impairs lysosome clearance causing SNCA/alpha-synuclein accumulation in neurons.

Autophagy 2021 Apr 23:1-15. Epub 2021 Apr 23.

Molecular Studies of Neurodegenerative Diseases Lab, FELS Cancer Institute for Personalized Medicine and Department of Neurology Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.

Despite the promising therapeutic effects of combinatory antiretroviral therapy (cART), 20% to 30% of HIV/AIDS patients living with long term infection still exhibit related cognitive and motor disorders. Clinical studies in HIV-infected patients revealed evidence of basal ganglia dysfunction, tremors, fine motor movement deficits, gait, balance, and increased risk of falls. Among older HIV adults, the frequency of cases with SNCA/α-synuclein staining is higher than in older healthy persons and may predict an increased risk of developing a neurodegenerative disease. Read More

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Bidirectional interconversion between PtdIns4P and PtdIns(4,5)P is required for autophagic lysosome reformation and protection from skeletal muscle disease.

Autophagy 2021 Apr 20:1-3. Epub 2021 Apr 20.

Cancer Program, and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia.

Autophagic lysosome reformation (ALR) recycles autolysosome membranes formed during autophagy, to make lysosomes and is essential for continued autophagy function. Localized membrane remodeling on autolysosomes leads to the extension of reformation tubules, which undergo scission to form new lysosomes. The phosphoinositides phosphatidylinositol-4-phosphate (PtdIns4P) and phosphatidylinositol-4,5-bisphosphate (PtdIns[4,5]P) induce this remodeling by recruiting protein effectors to membranes. Read More

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Macropinocytosis: the big drinker behind cancer cell self-consumption.

Autophagy 2021 Apr 27:1-2. Epub 2021 Apr 27.

Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California San Diego, La Jolla, CA, USA.

Poorly vascularized tumors embedded within a thick desmoplastic stroma, like pancreatic ductal adenocarcinoma (PDAC), are nutritionally stressed. Such tumors are also hypoxic and rely on a number of adaptive responses, including macroautophagy/autophagy and macropinocytosis (MP), to support their bioenergetic needs. Whereas autophagy enables starved cells to recycle intracellular macromolecules via lysosomal degradation and use the liberated amino acids (AA) to fuel their metabolism, MP allows cells to take up extracellular proteins via fluid-phase endocytosis and use them as an energy source. Read More

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Autophagy promotes mitochondrial respiration by providing serine for one-carbon-metabolism.

Autophagy 2021 Apr 18:1-4. Epub 2021 Apr 18.

Institute of Biochemistry and Molecular Biology I, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.

Whether macroautophagy/autophagy is physiologically relevant to regulate mitochondrial function for a rapid and dynamic adaptation of yeast cells to respiratory growth was not fully understood until recently. May . (2020. Read More

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HBx induces hepatocellular carcinogenesis through ARRB1-mediated autophagy to drive the G/S cycle.

Autophagy 2021 Apr 27:1-19. Epub 2021 Apr 27.

Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, China.

The hepatitis B virus X protein (HBx) is involved in the process of hepatocellular carcinoma via the activation of various oncogenes. Our previous study indicated that ARBB1 (arrestin beta 1) promotes hepatocellular carcinogenesis (HCC). However, the role of ARRB1 in HBx-related HCC remains unclear. Read More

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WLS/wntless is essential in controlling dendritic cell homeostasis via a WNT signaling-independent mechanism.

Autophagy 2021 Apr 14:1-16. Epub 2021 Apr 14.

Department of Respirology & Allergy, Third Affiliated Hospital of Shenzhen University, Shenzhen, China.

We propose that beyond its role in WNT secretion, WLS/GPR177 (wntless, WNT ligand secretion mediator) acts as an essential regulator controlling protein glycosylation, endoplasmic reticulum (ER) homeostasis, and dendritic cell (DC)-mediated immunity. WLS deficiency in bone marrow-derived DCs (BMDCs) resulted in poor growth and an inability to mount cytokine and T-cell responses , phenotypes that were irreversible by the addition of exogenous WNTs. In fact, WLS was discovered to integrate a protein complex in N-glycan-dependent and WLS domain-selective manners, comprising ER stress sensors and lectin chaperones. Read More

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Augmenting ATG14 alleviates atherosclerosis and inhibits inflammation via promotion of autophagosome-lysosome fusion in macrophages.

Autophagy 2021 May 4:1-13. Epub 2021 May 4.

Department of Cardiovascular Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.

Dysfunction of macroautophagy/autophagy in macrophages contributes to atherosclerosis. Impaired autophagy-lysosomal degradation system leads to lipid accumulation, facilitating atherosclerotic plaque. ATG14 is an essential regulator for the fusion of autophagosomes with lysosomes. Read More

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Direct homophilic interaction of LAMP2A with the two-domain architecture revealed by site-directed photo-crosslinks and steric hindrances in mammalian cells.

Autophagy 2021 Apr 14:1-19. Epub 2021 Apr 14.

Department of Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

LAMP1 (lysosomal-associated membrane protein 1) and LAMP2 are the most abundant protein components of lysosome membranes. Both LAMPs have common structures consisting of a large lumenal domain composed of two domains (N-domain and C-domain, which are membrane-distal and -proximal, respectively), both with the β-prism fold, a transmembrane domain, and a short cytoplasmic tail. LAMP2 is involved in various aspects of autophagy, and reportedly forms high-molecular weight complexes at the lysosomal membrane. Read More

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, one gene associated with multiple neurodevelopmental disorders.

Autophagy 2021 Apr 12:1-16. Epub 2021 Apr 12.

Department of Biomedical Sciences of Cells & Systems, Molecular Cell Biology Section, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

The gene is localized on the X-chromosome and variants in this gene are linked to six different neurodegenerative disorders, i.e., ß-propeller protein associated neurodegeneration, Rett-like syndrome, intellectual disability, and epileptic encephalopathies including developmental and epileptic encephalopathy, early-onset epileptic encephalopathy and West syndrome and potentially also specific malignancies. Read More

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Ferritinophagy is involved in the zinc oxide nanoparticles-induced ferroptosis of vascular endothelial cells.

Autophagy 2021 Apr 12:1-20. Epub 2021 Apr 12.

College of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China.

Zinc oxide nanoparticles (ZnONPs) hold great promise for biomedical applications. Previous studies have revealed that ZnONPs exposure can induce toxicity in endothelial cells, but the underlying mechanisms have not been fully elucidated. In this study, we report that ZnONPs can induce ferroptosis of both HUVECs and EA. Read More

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Combination of autophagy and NFE2L2/NRF2 activation as a treatment approach for neuropathic pain.

Autophagy 2021 Apr 9:1-21. Epub 2021 Apr 9.

Department of Anesthesiology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai 200003, China.

Macroautophagy/autophagy, an evolutionarily conserved process, plays an important role in the regulation of immune inflammation and nervous system homeostasis. However, the exact role and mechanism of autophagy in pain is still unclear. Here, we showed that impaired autophagy flux mainly occurred in astrocytes during the maintenance of neuropathic pain. Read More

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