PXD016095 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Chronic intermittent autophagy inhibition ameliorates Bag3-dependent cardiomyopathy |
Description | Mutations in the Hsp70 co-chaperone Bcl2-associated athanogene 3 (Bag3) result in myofibrillar myopathy and pediatric hypertrophic cardiomyopathy (pHCM) in human patients, but the pathological mechanisms underlying Bag3 dysfunction in the developing heart have remained unclear. Here we show that conditional ablation of Bag3 in cardiomyocytes (CMs) results in progressive cardiomyopathy accompanied by increased autophagic flux and autophagosome accumulation in the early post-natal period. Autophagy inhibition via acute administration of chloroquine (CQ) results in transient accumulation of cardiac proteins in the detergent-insoluble fraction, implying a role for autophagy in the degradation of unfolded proteins in the absence of Bag3 co-chaperone activity. Exacerbated autophagy in Bag3 deficient CMs leads to decreased soluble levels of proteins involved in cardiac contraction and conduction, including the gap junction protein connexin 43 (Cx43). Importantly, chronic CQ treatment during the early post-natal period results in a significant amelioration of the pathological phenotype, with recovered contractile performances and restoration of soluble levels of autophagy-targeted proteins. We therefore conclude that loss of Bag3 in CMs leads to autophagic flux exacerbation and that CQ treatment is relevant to therapeutic strategies for Bag3-dependent pHCM patients. |
HostingRepository | PRIDE |
AnnounceDate | 2024-06-05 |
AnnouncementXML | Submission_2024-06-05_08:44:23.385.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Johannes Graumann |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-10-31 04:22:41 | ID requested | |
⏵ 1 | 2024-06-05 08:44:23 | announced | |
Publication List
Keyword List
curator keyword: Biological |
submitter keyword: Chloroquine, Cx43, Bag3, Pediatric Hypertrophic Cardiomyopathy (pHCM),Autophagy, Protein Quality Control |
Contact List
Johnny Kim |
contact affiliation | Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research |
contact email | johnny.kim@mpi-bn.mpg.de |
lab head | |
Johannes Graumann |
contact affiliation | Institute of Translational Proteomics, Faculty of Medicine, Philipps-Universität Marburg |
contact email | johannes.graumann@uni-marburg.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
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- PRIDE
- PXD016095
- Label: PRIDE project
- Name: Chronic intermittent autophagy inhibition ameliorates Bag3-dependent cardiomyopathy