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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Recent advances in smart stimuli-responsive biomaterials for bone therapeutics and regeneration

Bone Research, Journal Year: 2022, Volume and Issue: 10(1)

Published: Feb. 23, 2022

Abstract Bone defects combined with tumors, infections, or other bone diseases are challenging in clinical practice. Autologous and allogeneic grafts two main traditional remedies, but they can cause a series of complications. To address this problem, researchers have constructed various implantable biomaterials. However, the original pathological microenvironment defects, such as residual severe infection, diseases, could further affect regeneration. Thus, rational design versatile biomaterials integrated therapy regeneration functions is great demand. Many strategies been applied to fabricate smart stimuli-responsive materials for regeneration, stimuli related external physical triggers endogenous disease microenvironments involving multiple strategies. Typical include light irradiation, electric magnetic fields, ultrasound, mechanical stimuli. These transform internal atomic packing arrangements cell fate, thus enhancing tissue In addition strategy, some specific microenvironments, excess reactive oxygen species mild acidity pH reduction enzymes secreted by bacteria electronegative potential defect sites, be used biochemical activate Herein, we summarize discuss construction therapeutic regenerative functions. The mechanisms, applications, existing limitations newly designed also clarified.

Language: Английский

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The role of autophagy in bone metabolism and clinical significance

Autophagy, Journal Year: 2023, Volume and Issue: 19(9), P. 2409 - 2427

Published: March 2, 2023

The skeletal system is the basis of vertebral body composition, which affords stabilization sites for muscle attachment, protects vital organs, stores mineral ions, supplies places to hematopoietic system, and participates in complex endocrine immune system. Not surprisingly, bones are constantly reabsorbed, formed, remodeled under physiological conditions. Once bone metabolic homeostasis interrupted (including inflammation, tumors, fractures, diseases), rapidly initiates regeneration maintain tissue structure quality. Macroautophagy/autophagy an essential process eukaryotic cells, maintains energy plays a role by controlling molecular degradation organelle renewal. One relatively new observation that mesenchymal osteoblasts, osteoclasts, osteocytes, chondrocytes, vascularization exhibit autophagy, mechanisms targets involved being explored updated. autophagy also emerging degenerative diseases (intervertebral disc degeneration [IVDD], osteoarthritis [OA], etc.) (osteoporosis [OP], osteitis deformans, osteosclerosis). use regulators modulate has benefited regeneration, including MTOR (mechanistic target rapamycin kinase) inhibitors, AMPK activators, phytochemicals. application biomaterials (especially nanomaterials) trigger attractive research direction, can exert superior therapeutic properties from material-loaded molecules/drugs or material's such as shape, roughness, surface chemistry, etc. All these have clinical significance with discovery associated signals, pathways, mechanisms, treatments future.Abbreviations: Δψm: mitochondrial transmembrane potential AMPK: AMP-activated protein kinase ARO: autosomal recessive osteosclerosis ATF4: activating transcription factor 4 ATG: autophagy-related β-ECD: β-ecdysone BMSC: marrow stem cell ER: endoplasmic reticulum FOXO: forkhead box O GC: glucocorticoid HIF1A/HIF-1α: hypoxia inducible 1 subunit alpha HSC: HSP: heat shock IGF1: insulin like growth IL1B/IL-1β: interleukin beta IVDD: intervertebral LPS: lipopolysaccharide MAPK: mitogen-activated MSC: MTOR: mechanistic NP: nucleus pulposus NPWT: negative pressure wound therapy OA: OP: osteoporosis PTH: parathyroid hormone ROS: reactive oxygen species SIRT1: sirtuin SIRT3: 3 SQSTM1/p62: sequestosome TNFRSF11B/OPG: TNF receptor superfamily member 11b TNFRSF11A/RANK: tumor necrosis superfamily, 11a TNFSF11/RANKL: (ligand) 11 TSC1: tuberous sclerosis ULK1: unc-51

Language: Английский

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The Role of Osteoclast Energy Metabolism in the Occurrence and Development of Osteoporosis

Frontiers in Endocrinology, Journal Year: 2021, Volume and Issue: 12

Published: May 12, 2021

In recent decades, the mechanism underlying bone metabolic disorders based on energy metabolism has been heavily researched. Bone resorption by osteoclasts plays an important role in occurrence and development of osteoporosis. However, osteoclast disorder that interferes with homeostasis not determined. is a process consumes large amounts adenosine triphosphate (ATP) produced glycolysis oxidative phosphorylation. addition to glucose, fatty acids amino can also be used as substrates produce through this review, we summarize analyze energy-based phenotypic changes, epigenetic regulation, coupling systemic during progression At same time, propose hypothesis, compensatory recovery (involving balance between survival functional activation), which may provide new approach for treatment

Language: Английский

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Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging

Aging Cell, Journal Year: 2024, Volume and Issue: 23(4)

Published: Jan. 29, 2024

Abstract Osteoarthritis (OA), a chronic degenerative joint disease, is highly prevalent among the aging population, and often leads to pain, disability, diminished quality of life. Although considerable research has been conducted, precise molecular mechanisms propelling OA pathogenesis continue be elusive, thereby impeding development effective therapeutics. Notably, recent studies have revealed subchondral bone lesions precede cartilage degeneration in early stage OA. This marked by escalated osteoclast‐mediated resorption, subsequent imbalances metabolism, accelerated turnover, decrease volume, contributing significantly pathological changes. While role hallmarks extensively elucidated from perspective chondrocytes, their connection with osteoclasts not yet fully understood. There compelling evidence suggest that age‐related abnormalities such as epigenetic alterations, proteostasis network disruption, cellular senescence, mitochondrial dysfunction, can stimulate osteoclast activity. review intends systematically discuss how contribute pathogenesis, placing particular emphasis on age‐induced shifts It also aims future probing into therapeutic approaches targeting during aging.

Language: Английский

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Autophagy receptor OPTN (optineurin) regulates mesenchymal stem cell fate and bone-fat balance during aging by clearing FABP3

Autophagy, Journal Year: 2020, Volume and Issue: 17(10), P. 2766 - 2782

Published: Nov. 4, 2020

Senile osteoporosis (OP) is often concomitant with decreased autophagic activity. OPTN (optineurin), a macroautophagy/autophagy (hereinafter referred to as autophagy) receptor, found play pivotal role in selective autophagy, coupling autophagy bone metabolism. However, its osteogenesis still mysterious. Herein, we identified Optn critical molecule of cell fate decision for marrow mesenchymal stem cells (MSCs), whose expression aged mice. Aged mice revealed osteoporotic loss, elevated senescence MSCs, osteogenesis, and enhanced adipogenesis, well optn–/ – Importantly, restoring by transplanting wild-type MSCs or infecting Optn-containing lentivirus rescued loss. The introduction loss-of-function mutant OptnK193R failed reestablish bone-fat balance. We further FABP3 (fatty acid binding protein 3, muscle heart) novel substrate OPTN. promoted adipogenesis inhibited MSCs. Knockdown alleviated loss Our study that reduced during aging might lead OP due lack degradation via autophagy. accumulation impaired leading the occurrence OP. Thus, reactivating inhibiting would open new avenue treat senile OP.Abbreviations: ADIPOQ: adiponectin, C1Q collagen domain containing; ALPL: alkaline phosphatase, liver/bone/kidney; BGLAP/OC/osteocalcin: gamma carboxyglutamate protein; BFR/BS: formation rate/bone surface; CALCOCO2/NDP52: calcium coiled-coil 2; CDKN1A/p21: cyclin-dependent kinase inhibitor 1A; CDKN2A/p16: cyclin dependent 2A; CDKN2B/p15: 2B; CEBPA: CCAAT/enhancer (C/EBP), alpha; COL1A1: collagen, type I, alpha 1; Ct. BV/TV: cortical volume fraction; Th: thickness; Es. Pm: endocortical perimeter; FABP4/Ap2: fatty 4, adipocyte; H2AX: H2A.X variant histone; HE: hematoxylin eosin; MAP1LC3B: microtubule-associated 1 light chain 3 beta; MAR: mineral apposition rate; MSCs: cells; NBR1: NBR1, cargo receptor; OP: osteoporosis; OPTN: optineurin; PDB: Paget disease bone; PPARG: peroxisome proliferator activated receptor gamma; Ps. periosteal qRT-PCR: quantitative real-time PCR; γH2AX: Phosphorylation Serine residue H2AX; ROS: reactive oxygen species; RUNX2: runt related transcription factor SA-GLB1: senescence-associated (SA)-GLB1 (galactosidase, beta 1); SP7/Osx/Osterix: Sp7 7; SQSTM1/p62: sequestosome TAX1BP1: Tax1 (human T leukemia virus I) Tb. trabecular N: number; Sp: separation; μCT: micro computed tomography.

Language: Английский

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Parathyroid hormone and its related peptides in bone metabolism

Biochemical Pharmacology, Journal Year: 2021, Volume and Issue: 192, P. 114669 - 114669

Published: July 2, 2021

Language: Английский

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Osteoclasts protect bone blood vessels against senescence through the angiogenin/plexin-B2 axis

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: March 23, 2021

Synthetic glucocorticoids (GCs), one of the most effective treatments for chronic inflammatory and autoimmune conditions in children, have adverse effects on growing skeleton. GCs inhibit angiogenesis bone, but underlying mechanisms remain unclear. Here, we show that GC treatment young mice induces vascular endothelial cell senescence metaphysis long inhibition improves GC-impaired bone with coupled osteogenesis. We identify angiogenin (ANG), a ribonuclease pro-angiogenic activity, secreted by osteoclasts as key factor protecting neighboring cells against senescence. ANG maintains proliferative activity through plexin-B2 (PLXNB2)-mediated transcription ribosomal RNA (rRNA). inhibits production suppressing osteoclast formation metaphysis, resulting impaired rRNA subsequent cellular These findings reveal role metaphyseal blood vessel mediating action skeleton establish ANG/PLXNB2 axis molecular basis osteoclast-vascular interplay skeletal angiogenesis.

Language: Английский

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High proportion strontium-doped micro-arc oxidation coatings enhance early osseointegration of titanium in osteoporosis by anti-oxidative stress pathway

Bioactive Materials, Journal Year: 2021, Volume and Issue: 10, P. 405 - 419

Published: Aug. 31, 2021

The excessive accumulation of reactive oxygen species (ROS) under osteoporosis precipitates a microenvironment with high levels oxidative stress (OS). This could significantly interfere the bioactivity conventional titanium implants, impeding their early osseointegration bone. We have prepared series strontium (Sr)-doped implants via micro-arc oxidation (MAO) to verify efficacy and differences in osteoinduction capabilities normal osteoporotic (high OS levels) conditions. Apart from chemical composition, all groups exhibited similar physicochemical properties (morphology, roughness, crystal structure, wettability). Among groups, low Sr group (Sr25%) was more conducive osteogenesis In contrast, by increasing catalase (CAT)/superoxide dismutase (SOD) activity decreasing ROS levels, Sr-doped samples (Sr75% Sr100%) were superior Sr25% inducing osteogenic differentiation MC3T3-E1 cells M2 phenotype polarization RAW264.7 cells, thus enhancing osseointegration. Furthermore, results both vitro cell co-culture vivo studies also showed that (especially had positive effects on osteoimmunomodulation microenvironment. Ultimately, collated findings indicated proportion MAO coatings favorable for patients implant restorations.

Language: Английский

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Degradation of the NOTCH intracellular domain by elevated autophagy in osteoblasts promotes osteoblast differentiation and alleviates osteoporosis

Autophagy, Journal Year: 2022, Volume and Issue: 18(10), P. 2323 - 2332

Published: Jan. 13, 2022

Maintenance of bone integrity is mediated by the balanced actions osteoblasts and osteoclasts. Because macroautophagy/autophagy regulates osteoblast mineralization, osteoclast differentiation, their secretion from cells, autophagy deficiency in or osteoclasts can disrupt this balance. However, it remains unclear whether upregulation becomes beneficial for suppression bone-associated diseases. In study, we found that genetic facilitated formation. We generated mice which was specifically upregulated deleting gene encoding RUBCN/Rubicon, a negative regulator autophagy. The rubcnflox/flox;Sp7/Osterix-Cre showed progressive skeletal abnormalities femur bones. Consistent with this, RUBCN resulted elevated differentiation as well an increase expression key transcription factors involved function such Runx2 Bglap/Osteocalcin. Furthermore, accelerated autophagic degradation NOTCH intracellular domain (NICD) downregulated signaling pathway, negatively differentiation. Notably, osteoblast-specific deletion alleviated phenotype mouse model osteoporosis. conclude homeostasis. On basis these findings, propose medications targeting NICD could be used to treat age-related osteoporosis fracture.

Language: Английский

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