ArticleThe Journal of clinical investigation2014
Atrogin-1 deficiency promotes cardiomyopathy and premature death via impaired autophagy.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
78 citing papers in PubMed, 143 citations in OpenAlex.
- The hallmarks of skeletal muscle health.Nature metabolism · 2026Review
- FAP PET identifies earlycardiac molecular changesinduced by doxorubicin chemotherapy.JCI insight · 2025Article
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- Cardiac sympathetic neurons are additional cells affected in genetically determined arrhythmogenic cardiomyopathy.The Journal of physiology · 2025Article
- The multifaceted role of autophagy and mitophagy in cardiovascular health and disease.Autophagy reports · 2025Review
- Mechanistic insights into fasting-induced autophagy in the aging heart.World journal of cardiology · 2024Article
- Atrogin-1 promotes muscle homeostasis by regulating levels of endoplasmic reticulum chaperone BiP.JCI insight · 2024Article
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- Hypertrophic cardiomyopathy inThe journal of cardiovascular aging · 2024Article
- From cancer therapy to cardiac safety: the role of proteostasis in drug-induced cardiotoxicity.Frontiers in pharmacology · 2024Review
- Autophagy in Heart Failure: Insights into Mechanisms and Therapeutic Implications.Journal of cardiovascular development and disease · 2023Review
- Impact of polyphenols on heart failure and cardiac hypertrophy: clinical effects and molecular mechanisms.Frontiers in cardiovascular medicine · 2023Review
- Neurotoxic Effect of Doxorubicin Treatment on Cardiac Sympathetic Neurons.International journal of molecular sciences · 2022Article
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- SIRT6 Protects Against Myocardial Ischemia-Reperfusion Injury by Attenuating Aging-Related CHMP2B Accumulation.Journal of cardiovascular translational research · 2022Article
- Nerve growth factor transfer from cardiomyocytes to innervating sympathetic neurons activates TrkA receptors at the neuro-cardiac junction.The Journal of physiology · 2022Article
- Roles of Cullin-RING Ubiquitin Ligases in Cardiovascular Diseases.Biomolecules · 2022Review
- Obstructive Sleep Apnea Impacts Cardiac Function in Dilated Cardiomyopathy Patients Through Circulating Exosomes.Frontiers in cardiovascular medicine · 2022Article
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18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Cardiomyocyte proteostasis is mediated by the ubiquitin/proteasome system (UPS) and autophagy/lysosome system and is fundamental for cardiac adaptation to both physiologic (e.g., exercise) and pathologic (e.g., pressure overload) stresses. Both the UPS and autophagy/lysosome system exhibit reduced efficiency as a consequence of aging, and dysfunction in these systems is associated with cardiomyopathies. The muscle-specific ubiquitin ligase atrogin-1 targets signaling proteins involved in cardiac hypertrophy for degradation. Here, using atrogin-1 KO mice in combination with in vivo pulsed stable isotope labeling of amino acids in cell culture proteomics and biochemical and cellular analyses, we identified charged multivesicular body protein 2B (CHMP2B), which is part of an endosomal sorting complex (ESCRT) required for autophagy, as a target of atrogin-1-mediated degradation. Mice lacking atrogin-1 failed to degrade CHMP2B, resulting in autophagy impairment, intracellular protein aggregate accumulation, unfolded protein response activation, and subsequent cardiomyocyte apoptosis, all of which increased progressively with age. Cellular proteostasis alterations resulted in cardiomyopathy characterized by myocardial remodeling with interstitial fibrosis, with reduced diastolic function and arrhythmias. CHMP2B downregulation in atrogin-1 KO mice restored autophagy and decreased proteotoxicity, thereby preventing cell death. These data indicate that atrogin-1 promotes cardiomyocyte health through mediating the interplay between UPS and autophagy/lysosome system and its alteration promotes development of cardiomyopathies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.