Cardiac fibroblasts regulate the development of heart failure via Htra3-TGF-β-IGFBP7 axis DOI Creative Commons
Toshiyuki Ko, Seitaro Nomura, Shintaro Yamada

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: June 7, 2022

Abstract Tissue fibrosis and organ dysfunction are hallmarks of age-related diseases including heart failure, but it remains elusive whether there is a common pathway to induce both events. Through single-cell RNA-seq, spatial transcriptomics, genetic perturbation, we elucidate that high-temperature requirement A serine peptidase 3 (Htra3) critical regulator cardiac failure by maintaining the identity quiescent fibroblasts through degrading transforming growth factor-β (TGF-β). Pressure overload downregulates expression Htra3 in activated TGF-β signaling, which induces not only also DNA damage accumulation secretory phenotype induction failing cardiomyocytes. Overexpression inhibits signaling ameliorates after pressure overload. Htra3-regulated spatio-temporal cardiomyocyte observed specifically infarct regions myocardial infarction. Integrative analyses single-cardiomyocyte transcriptome plasma proteome human reveal IGFBP7, cytokine downstream secreted from cardiomyocytes, most predictable marker advanced failure. These findings highlight roles regulating homeostasis Htra3-TGF-β-IGFBP7 pathway, would be therapeutic target for

Language: Английский

Hallmarks of aging: An expanding universe DOI Creative Commons
Carlos López‐Otín, Marı́a A. Blasco, Linda Partridge

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(2), P. 243 - 278

Published: Jan. 1, 2023

Language: Английский

Citations

2710
Autophagy in major human diseases DOI Creative Commons
Daniel J. Klionsky, Giulia Petroni, Ravi K. Amaravadi

et al.

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

Citations

1064
Immunogenic cell stress and death DOI Open Access
Guido Kroemer,

Claudia Galassi,

Laurence Zitvogel

et al.

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(4), P. 487 - 500

Published: Feb. 10, 2022

Language: Английский

Citations

826
Faulty autolysosome acidification in Alzheimer’s disease mouse models induces autophagic build-up of Aβ in neurons, yielding senile plaques DOI Creative Commons
Ju‐Hyun Lee, Dun‐Sheng Yang, Chris N. Goulbourne

et al.

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(6), P. 688 - 701

Published: June 1, 2022

Autophagy is markedly impaired in Alzheimer's disease (AD). Here we reveal unique autophagy dysregulation within neurons five AD mouse models vivo and identify its basis using a neuron-specific transgenic mRFP-eGFP-LC3 probe of pH, multiplex confocal imaging correlative light electron microscopy. Autolysosome acidification declines well before extracellular amyloid deposition, associated with lowered vATPase activity build-up Aβ/APP-βCTF selectively enlarged de-acidified autolysosomes. In more compromised yet still intact neurons, profuse Aβ-positive autophagic vacuoles (AVs) pack into large membrane blebs forming flower-like perikaryal rosettes. This pattern, termed PANTHOS (poisonous anthos (flower)), also present brains. Additional AVs coalesce peri-nuclear networks tubules where fibrillar β-amyloid accumulates intraluminally. Lysosomal permeabilization, cathepsin release lysosomal cell death ensue, accompanied by microglial invasion. Quantitative analyses confirm that individual exhibiting are the principal source senile plaques precursor protein models.

Language: Английский

Citations

425
p53 in ferroptosis regulation: the new weapon for the old guardian DOI Open Access
Yanqing Liu, Wei Gu

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: 29(5), P. 895 - 910

Published: Jan. 27, 2022

Language: Английский

Citations

336
Mitochondrial signal transduction DOI Creative Commons
Martin Picard, Orian S. Shirihai

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(11), P. 1620 - 1653

Published: Nov. 1, 2022

The analogy of mitochondria as powerhouses has expired. Mitochondria are living, dynamic, maternally inherited, energy-transforming, biosynthetic, and signaling organelles that actively transduce biological information. We argue the processor cell, together with nucleus other they constitute mitochondrial information processing system (MIPS). In a three-step process, (1) sense respond to both endogenous environmental inputs through morphological functional remodeling; (2) integrate network-based physical interactions diffusion mechanisms; (3) produce output signals tune functions systemically regulate physiology. This input-to-output transformation allows metabolic, biochemical, neuroendocrine, local or systemic enhance organismal adaptation. An explicit focus on signal transduction emphasizes role communication in biology. framework also opens new avenues understand how mediate inter-organ processes underlying human health.

Language: Английский

Citations

320
Gut barrier disruption and chronic disease DOI
Jan Martel, Shih-Hsin Chang,

Yun‐Fei Ko

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2022, Volume and Issue: 33(4), P. 247 - 265

Published: Feb. 9, 2022

Language: Английский

Citations

293
Meta-hallmarks of aging and cancer DOI Creative Commons
Carlos López‐Otín, Federico Pietrocola, David Roiz‐Valle

et al.

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(1), P. 12 - 35

Published: Jan. 1, 2023

Language: Английский

Citations

263
Organelle-specific regulation of ferroptosis DOI Open Access
Xin Chen, Rui Kang, Guido Kroemer

et al.

Cell Death and Differentiation, Journal Year: 2021, Volume and Issue: 28(10), P. 2843 - 2856

Published: Aug. 31, 2021

Language: Английский

Citations

250
The landscape of aging DOI Open Access
Yusheng Cai, Wei Song, Jiaming Li

et al.

Science China Life Sciences, Journal Year: 2022, Volume and Issue: 65(12), P. 2354 - 2454

Published: Sept. 2, 2022

Language: Английский

Citations

239