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Citations to this article

Atrogin-1 deficiency promotes cardiomyopathy and premature death via impaired autophagy
Tania Zaglia, … , Marco Mongillo, Marco Sandri
Tania Zaglia, … , Marco Mongillo, Marco Sandri
Published May 1, 2014
Citation Information: J Clin Invest. 2014;124(6):2410-2424. https://doi.org/10.1172/JCI66339.
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Research Article Cardiology Article has an altmetric score of 20

Atrogin-1 deficiency promotes cardiomyopathy and premature death via impaired autophagy

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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.

Authors

Tania Zaglia, Giulia Milan, Aaron Ruhs, Mauro Franzoso, Enrico Bertaggia, Nicola Pianca, Andrea Carpi, Pierluigi Carullo, Paola Pesce, David Sacerdoti, Cristiano Sarais, Daniele Catalucci, Marcus Krüger, Marco Mongillo, Marco Sandri

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2009 Total
Citations: 1 6 2 7 15 6 4 7 4 13 6 1 1 73
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2009 (1)

Title and authors Publication Year
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2009

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