Autophagy in major human diseases

The EMBO Journal, Journal Year: 2021, Volume and Issue: 40(19)

Published: Aug. 30, 2021

Review30 August 2021Open Access Autophagy in major human diseases Daniel J Klionsky orcid.org/0000-0002-7828-8118 Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA Search for more papers by this author Giulia Petroni Department Radiation Oncology, Weill Cornell Medical College, New York, NY, Ravi K Amaravadi Medicine, Pennsylvania, Philadelphia, PA, Abramson Cancer Center, Eric H Baehrecke Molecular, Cell and Biology, Massachusetts School, Worcester, MA, Andrea Ballabio orcid.org/0000-0003-1381-4604 Telethon Institute Genetics Pozzuoli, Italy Translational Sciences, Section Pediatrics, Federico II University, Naples, Molecular Human Genetics, Baylor College Jan Dan Duncan Neurological Research Texas Children Hospital, Houston, TX, Patricia Boya orcid.org/0000-0003-3045-951X Margarita Salas Center Biological Research, Spanish National Council, Madrid, Spain José Manuel Bravo-San Pedro Faculty Physiology, Complutense Networked Biomedical Neurodegenerative Diseases (CIBERNED), Ken Cadwell Kimmel Biology Medicine at the Skirball York Grossman School Microbiology, Division Gastroenterology Hepatology, Langone Health, Francesco Cecconi orcid.org/0000-0002-5614-4359 Stress Survival Unit, Autophagy, Recycling Disease (CARD), Danish Society Copenhagen, Denmark Pediatric Onco-Hematology Gene Therapy, IRCCS Bambino Gesù Children's Rome, Rome 'Tor Vergata', Augustine M Choi Pulmonary Critical Care Joan Sanford I. York-Presbyterian Mary E Nephrology Hypertension, Charleen T Chu orcid.org/0000-0002-5052-8271 Pathology, Pittsburgh Pittsburgh, Patrice Codogno orcid.org/0000-0002-5492-3180 Institut Necker-Enfants Malades, INSERM U1151-CNRS UMR 8253, Paris, France Université de Maria Isabel Colombo Laboratorio Mecanismos Moleculares Implicados en el Tráfico Vesicular y la Autofagia-Instituto Histología Embriología (IHEM)-Universidad Nacional Cuyo, CONICET- Facultad Ciencias Médicas, Mendoza, Argentina Ana Cuervo orcid.org/0000-0002-0771-700X Developmental Albert Einstein Bronx, Aging Studies, Vojo Deretic Inflammation Metabolism (AIM, Excellence, Mexico Health Albuquerque, NM, Ivan Dikic orcid.org/0000-0001-8156-9511 Biochemistry II, Goethe Frankfurt, Frankfurt am Main, Germany Buchmann Zvulun Elazar Biomolecular The Weizmann Science, Rehovot, Israel Eeva-Liisa Eskelinen Biomedicine, Turku, Finland Gian Fimia orcid.org/0000-0003-4438-3325 Sapienza Epidemiology, Preclinical Advanced Diagnostics, Infectious 'L. Spallanzani' IRCCS, David A Gewirtz orcid.org/0000-0003-0437-4934 Pharmacology Toxicology, Virginia Commonwealth Richmond, VA, Douglas R Green Immunology, St. Jude Memphis, TN, Malene Hansen Burnham Prebys Discovery Program Development, Aging, Regeneration, La Jolla, CA, Marja Jäättelä orcid.org/0000-0001-5950-7111 Death Metabolism, & Disease, Cellular Terje Johansen orcid.org/0000-0003-1451-9578 Group, Tromsø—The Arctic Norway, Tromsø, Norway Gábor Juhász Szeged, Hungary Anatomy, Eötvös Loránd Budapest, Vassiliki Karantza Merck Co., Inc., Kenilworth, NJ, Claudine Kraft orcid.org/0000-0002-3324-4701 ZBMZ, Freiburg, CIBSS - Centre Integrative Signalling Guido Kroemer orcid.org/0000-0002-9334-4405 Recherche des Cordeliers, Equipe Labellisée par Ligue Contre le Cancer, Sorbonne Université, Inserm U1138, Universitaire France, Metabolomics Platforms, Gustave Roussy, Villejuif, Pôle Biologie, Hôpital Européen Georges Pompidou, AP-HP, Suzhou Systems Chinese Academy Suzhou, China Karolinska Women's Stockholm, Sweden Nicholas Ktistakis Programme, Babraham Cambridge, UK Sharad Kumar orcid.org/0000-0001-7126-9814 South Australia, Adelaide, SA, Australia Carlos Lopez-Otin orcid.org/0000-0001-6964-1904 Departamento Bioquímica Biología Medicina, Instituto Universitario Oncología del Principado Asturias (IUOPA), Universidad Oviedo, Centro Investigación Biomédica Red Cáncer (CIBERONC), Kay F Macleod Ben May Gordon W-338, Chicago, IL, Frank Madeo Biosciences, NAWI Graz, Austria BioTechMed-Graz, Field Excellence BioHealth – Jennifer Martinez Immunity, Laboratory, Environmental NIH, Triangle Park, NC, Alicia Meléndez Department, Queens City Flushing, Graduate PhD Programs Noboru Mizushima orcid.org/0000-0002-6258-6444 Tokyo, Japan Christian Münz orcid.org/0000-0001-6419-1940 Viral Immunobiology, Experimental Zurich, Switzerland Josef Penninger Biotechnology Austrian (IMBA), Vienna BioCenter (VBC), Vienna, British Columbia, Vancouver, BC, Canada Rushika Perera orcid.org/0000-0003-2435-2273 California, San Francisco, Helen Diller Family Comprehensive Mauro Piacentini orcid.org/0000-0003-2919-1296 "Tor Vergata", Laboratory Cytology Russian Saint Petersburg, Russia Fulvio Reggiori orcid.org/0000-0003-2652-2686 Cells Systems, Section, Groningen, Netherlands C Rubinsztein Cambridge Dementia Kevin Ryan Beatson Glasgow, Junichi Sadoshima Cardiovascular Rutgers Jersey Newark, Laura Santambrogio Sandra Edward Meyer Caryl Englander Precision Luca Scorrano orcid.org/0000-0002-8515-8928 Istituto Veneto di Medicina Molecolare, Padova, Hans-Uwe Simon Pharmacology, Bern, Clinical Immunology Allergology, Sechenov Moscow, Fundamental Kazan Federal Kazan, Anna Katharina Kennedy Rheumatology, NDORMS, Oxford, Anne Simonsen orcid.org/0000-0003-4711-7057 Basic Oslo, Reprogramming, Oslo Hospital Montebello, Alexandra Stolz orcid.org/0000-0002-3340-439X Nektarios Tavernarakis orcid.org/0000-0002-5253-1466 Biotechnology, Foundation Technology-Hellas, Heraklion, Crete, Greece Sharon Tooze orcid.org/0000-0002-2182-3116 Francis Crick London, Tamotsu Yoshimori orcid.org/0000-0001-9787-3788 Osaka Suita, Intracellular Membrane Dynamics, Frontier Integrated Science Division, Open Transdisciplinary Initiatives (OTRI), Junying Yuan Interdisciplinary on Chemistry, Shanghai Organic Shanghai, Harvard Boston, Zhenyu Yue Neurology, Friedman Brain Icahn Mount Sinai, Qing Zhong orcid.org/0000-0001-6979-955X Key Differentiation Apoptosis Ministry Education, Pathophysiology, Jiao Tong (SJTU-SM), Lorenzo Galluzzi Corresponding Author [email protected] orcid.org/0000-0003-2257-8500 Dermatology, Yale Haven, CT, Pietrocola orcid.org/0000-0002-2930-234X Biosciences Nutrition, Huddinge, mor

Language: Английский

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Mitochondria ROS and mitophagy in acute kidney injury

Autophagy, Journal Year: 2022, Volume and Issue: 19(2), P. 401 - 414

Published: June 9, 2022

Mitophagy is an essential mitochondrial quality control mechanism that eliminates damaged mitochondria and the production of reactive oxygen species (ROS). The relationship between oxidative stress, ROS mitophagy are intimately interwoven, these processes all involved in various pathological conditions acute kidney injury (AKI). elimination through mammals a complicated process which involves several pathways. Furthermore, interplay different types cell death, such as apoptosis, pyroptosis ferroptosis unclear. Here we will review recent advances our understanding mitophagy, pathways, relevance pathogenesis AKI.Abbreviations: AKI: injury; AMBRA1: autophagy beclin 1 regulator 1; ATP: adenosine triphosphate; BAK1: BCL2 antagonist/killer BAX: associated X, apoptosis regulator; BCL2: BECN1: BH3: homology domain 3; BNIP3: interacting protein BNIP3L/NIX: 3 like; CASP1: caspase CAT: catalase; CCCP: carbonyl cyanide m-chlorophenylhydrazone; CI-AKI: contrast-induced CISD1: CDGSH iron sulfur CL: cardiolipin; CNP: 2',3'-cyclic nucleotide 3'-phosphodiesterase; DNM1L/DRP1: dynamin E3: enzyme ETC: electron transport chain; FA: folic acid; FUNDC1: FUN14 containing G3P: glycerol-3-phosphate; G6PD: glucose-6-phosphate dehydrogenase; GPX: glutathione peroxidase; GSH: glutathione; GSK3B: glycogen synthase kinase beta; GSR: glutathione-disulfide reductase; HIF1A: hypoxia inducible factor subunit alpha; HUWE1: HECT, UBA WWE IL1B: interleukin IMM: inner membrane; IPC: ischemic preconditioning; IRI: ischemia-reperfusion LIR: LC3-interacting region; LPS: lipopolysaccharide; MA: malate-aspartate; MPT: permeability transition; MUL1: E3 ubiquitin ligase mtROS: ROS; NLR: NOD-like receptor; NLRP3: NLR family pyrin NOX: NADPH oxidase; OGD-R: oxygen-glucose deprivation-reperfusion; OMM: outer OPA1: OPA1 like GTPase; OXPHOS: phosphorylation; PARL: presenilin rhomboid PINK1: PTEN induced PLSCR3: phospholipid scramblase PMP: peptidase, processing; PRDX: peroxiredoxin; PRKN: parkin RBR ligase; RPTC: rat proximal tubular cells; ROS: species; SLC7A11/xCT: solute carrier 7 member 11; SOD: superoxide dismutase; SOR: SQSTM1/p62: sequestosome TCA: tricarboxylic TIMM: translocase TOMM: TXN: thioredoxin; VDAC: voltage dependent anion channel; VCP: valosin protein.

Language: Английский

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An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3651 - 3651

Published: March 26, 2022

Sodium-glucose co-transporter 2 (SGLT2) inhibitors block glucose reabsorption in the renal proximal tubule, an insulin-independent mechanism that plays a critical role glycemic regulation diabetes. In addition to their glucose-lowering effects, SGLT2 prevent both damage and onset of chronic kidney disease cardiovascular events, particular heart failure with reduced preserved ejection fraction. These unexpected benefits prompted changes treatment guidelines scientific interest underlying mechanisms. Aside from target effects inhibition, wide spectrum beneficial actions is described for heart, even though cardiac tissue does not express channels. Correction cardiorenal risk factors, metabolic adjustments ameliorating myocardial substrate utilization, optimization ventricular loading conditions through on diuresis, natriuresis, vascular function appear be main mechanisms observed protection. Additional clinical advantages associated using are antifibrotic due correction inflammation oxidative stress, modulation mitochondrial function, autophagy. Much research required understand numerous complex pathways involved inhibition. This review summarizes current known SGLT2-mediated

Language: Английский

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

Autophagy, Journal Year: 2022, Volume and Issue: 19(1), P. 256 - 277

Published: May 1, 2022

Following acute kidney injury (AKI), renal tubular cells may stimulate fibroblasts in a paracrine fashion leading to interstitial fibrosis, but the factors and their regulation under this condition remain elusive. Here we identify macroautophagy/autophagy-dependent FGF2 (fibroblast growth factor 2) production cells. Upon induction, acts as key activate for fibrosis. After ischemic AKI mice, autophagy activation persisted weeks In inducible, tubule-specific atg7 (autophagy related 7) knockout (iRT-atg7-KO) deficiency induced after suppressed pro-fibrotic phenotype reduced Among major cytokines, iRT-atg7-KO mice specifically diminished FGF2. Autophagy inhibition also attenuated expression TGFB1/TGF-β1 (transforming factor, beta 1)-treated Consistent with action, culture medium of TGFB1-treated stimulated fibroblasts, effect was by neutralizing antibody fgf2- or atg7-deletion human, compared non-AKI, biopsies from post-AKI patients had higher levels cells, which showed significant correlations These results indicate that persistent induces transformation secretion FGF2, activates fibrosis during maladaptive repair.Abbreviations: 3-MA: 3-methyladnine; ACTA2/α-SMA: actin alpha 2, smooth muscle, aorta; ACTB/β-actin: actin, beta; AKI: injury; ATG/Atg: related; BUN: blood urea nitrogen; CCN2/CTGF: cellular communication network 2; CDKN2A/p16: cyclin dependent kinase inhibitor 2A; CKD: chronic disease; CM: conditioned medium; COL1A1: collagen, type I, 1; COL4A1: IV, CQ: chloroquine; ECM: extracellular matrix; eGFR: estimated glomerular filtration rate; ELISA: enzyme-linked immunosorbent assay; FGF2: fibroblast FN1: fibronectin FOXO3: forkhead box O3; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HAVCR1/KIM-1: hepatitis A virus receptor IHC: immunohistochemistry; IRI: ischemia-reperfusion ISH: situ hybridization; LTL: lotus tetragonolobus lectin; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 MTOR: mechanistic target rapamycin kinase; PDGFB: platelet derived B polypeptide; PPIB/cyclophilin B: peptidylprolyl isomerase B; RT-qPCR: real time-quantitative PCR; SA-GLB1/β-gal: senescence-associated galactosidase, SASP: secretory phenotype; sCr: serum creatinine; SQSTM1/p62: sequestosome TASCC: TOR-autophagy spatial coupling compartment; TGFB1/TGF-β1: transforming VIM: vimentin.

Language: Английский

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Mechanisms of podocyte injury and implications for diabetic nephropathy

Clinical Science, Journal Year: 2022, Volume and Issue: 136(7), P. 493 - 520

Published: April 1, 2022

Abstract Albuminuria is the hallmark of both primary and secondary proteinuric glomerulopathies, including focal segmental glomerulosclerosis (FSGS), obesity-related nephropathy, diabetic nephropathy (DN). Moreover, albuminuria an important feature all chronic kidney diseases (CKDs). Podocytes play a key role in maintaining permselectivity glomerular filtration barrier (GFB) injury podocyte, leading to foot process (FP) effacement podocyte loss, unifying underlying mechanism glomerulopathies. The metabolic insult hyperglycemia paramount importance pathogenesis DN, while insults damage are poorly defined other However, shared mechanisms have been identified. Herein, we will review haemodynamic oxidative stress, inflammation, lipotoxicity, endocannabinoid (EC) hypertone, mitochondrial autophagic dysfunction damage, focussing particularly on their DN. Gaining better insight into may provide novel targets for treatment. strategies boosting repair open way regenerative medicine.

Language: Английский

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Comprehensive single-cell transcriptional profiling defines shared and unique epithelial injury responses during kidney fibrosis

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(12), P. 1977 - 1998.e9

Published: Oct. 19, 2022

Language: Английский

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Mitophagy alleviates cisplatin-induced renal tubular epithelial cell ferroptosis through ROS/HO-1/GPX4 axis

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(4), P. 1192 - 1210

Published: Jan. 1, 2023

Cisplatin is widely recommended in combination for the treatment of tumors, thus inevitably increasing incidence cisplatin-induced acute kidney injury. Mitophagy a type mitochondrial quality control mechanism that degrades damaged mitochondria and maintains cellular homeostasis. Ferroptosis, new modality programmed cell death, characterized by iron-dependent phospholipid peroxidation oxidative membrane damage. However, role mitophagy ferroptosis disease unclear. Here, we investigated underlying both BNIP3-mediated PINK1-PARK2-mediated mitophagy-induced attenuation The results showed cisplatin induced injury, ROS release, intracellular iron accumulation, lipid kidney, which were aggravated Bnip3 knockout, Pink1 knockout or Park2 cisplatin-treated mice. Ferrstatin-1, synthetic antioxidative inhibitor, rescued caused inhibition mitophagy. Thus, present study elucidated novel protects against renal tubular epithelial through ROS/HO1/GPX4 axis.

Language: Английский

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The Pathophysiology of Sepsis-Associated AKI

Clinical Journal of the American Society of Nephrology, Journal Year: 2022, Volume and Issue: 17(7), P. 1050 - 1069

Published: June 28, 2022

Sepsis-associated AKI is a life-threatening complication that associated with high morbidity and mortality in patients who are critically ill. Although it clear early supportive interventions sepsis reduce mortality, less they prevent or ameliorate sepsis-associated AKI. This likely because specific mechanisms underlying attributable to not fully understood. Understanding these will form the foundation for development of strategies diagnosis treatment Here, we summarize recent laboratory clinical studies, focusing on critical factors pathophysiology AKI: microcirculatory dysfunction, inflammation, NOD-like receptor protein 3 inflammasome, microRNAs, extracellular vesicles, autophagy efferocytosis, inflammatory reflex pathway, vitamin D, metabolic reprogramming. Lastly, identifying molecular targets defining subphenotypes permit precision approaches prevention

Language: Английский

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Intestinal Fibrosis in Inflammatory Bowel Disease and the Prospects of Mesenchymal Stem Cell Therapy

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 18, 2022

Intestinal fibrosis is an important complication of inflammatory bowel disease (IBD). In the course development fibrosis, certain parts intestine become narrowed, significantly destroying structure and function affecting quality life patients. Chronic inflammation initiating factor fibrosis. Unfortunately, existing anti-inflammatory drugs cannot effectively prevent alleviate there no effective anti-fibrotic drug, which makes surgical treatment mainstream for intestinal stenosis. Mesenchymal stem cells (MSCs) are capable tissue regeneration repair through their self-differentiation, secretion cytokines, extracellular vesicles. MSCs have been shown to play therapeutic role in many organs. However, MSC largely remained unexplored. This review summarizes mechanism including immune cells, TGF-β, gut microbiome metabolites. Available options particularly, also discussed.

Language: Английский

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Uncovering the mechanism of resveratrol in the treatment of diabetic kidney disease based on network pharmacology, molecular docking, and experimental validation

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: June 12, 2023

Abstract Background Diabetic kidney disease (DKD) has been the leading cause of chronic in developed countries. Evidence benefits resveratrol (RES) for treatment DKD is accumulating. However, comprehensive therapeutic targets and underlying mechanisms through which RES exerts its effects against are limited. Methods Drug were obtained from Drugbank SwissTargetPrediction Databases. Disease DisGeNET, Genecards, Therapeutic Target Database. identified by intersecting drug targets. GO functional enrichment analysis, KEGG pathway association analysis performed using DAVID database visualized Cytoscape software. Molecular docking validation binding capacity between was UCSF Chimera software SwissDock webserver. The high glucose (HG)-induced podocyte injury model, RT-qPCR, western blot used to verify reliability on target proteins. Results After intersection 86 566 targets, 25 obtained. And proteins classified into 6 categories. A total 11 cellular components terms 27 diseases, top 20 enriched biological processes, molecular functions, pathways potentially involved action recorded. studies showed that had a strong affinity toward PPARA, ESR1, SLC2A1, SHBG, AR, AKR1B1, PPARG, IGF1R, RELA, PIK3CA, MMP9, AKT1, INSR, MMP2, TTR, CYP2C9 domains. HG-induced model successfully constructed validated RT-qPCR blot. able reverse abnormal gene expression INSR. Conclusions may INSR domains act as agent DKD. These findings comprehensively reveal potential provide theoretical bases clinical application

Language: Английский

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