Fiche du document
- doi: 10.1111/acel.13715
- issn: 1474-9718
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1111/acel.13715
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/36259256
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1474-9726
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_8203798BCD094
info:eu-repo/semantics/openAccess , CC BY 4.0 , https://creativecommons.org/licenses/by/4.0/
Sujets proches
FlyCiter ce document
E.D. Papanagnou et al., « Autophagy activation can partially rescue proteasome dysfunction-mediated cardiac toxicity. », Serveur académique Lausannois, ID : 10.1111/acel.13715
Métriques
Partage / Export
Résumé
The ubiquitin-proteasome pathway and its functional interplay with other proteostatic and/or mitostatic modules are crucial for cell viability, especially in post-mitotic cells like cardiomyocytes, which are constantly exposed to proteotoxic, metabolic, and mechanical stress. Consistently, treatment of multiple myeloma patients with therapeutic proteasome inhibitors may induce cardiac failure; yet the effects promoted by heart-targeted proteasome dysfunction are not completely understood. We report here that heart-targeted proteasome knockdown in the fly experimental model results in increased proteome instability and defective mitostasis, leading to disrupted cardiac activity, systemic toxicity, and reduced longevity. These phenotypes were partially rescued by either heart targeted- or by dietary restriction-mediated activation of autophagy. Supportively, activation of autophagy by Rapamycin or Metformin administration in flies treated with proteasome inhibitors reduced proteome instability, partially restored mitochondrial function, mitigated cardiotoxicity, and improved flies' longevity. These findings suggest that autophagic inducers represent a novel promising intervention against proteasome inhibitor-induced cardiovascular complications.