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Consistently, treatment of multiple myeloma patients with therapeutic proteasome inhibitors may induce cardiac failure; yet the effects promoted by heart\u2010targeted proteasome dysfunction are not completely understood. We report here that heart\u2010targeted 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\u2010 or by dietary restriction\u2010mediated 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\u2010induced cardiovascular complications.<\/jats:p>","DOI":"10.1111\/acel.13715","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T07:56:23Z","timestamp":1666166183000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Autophagy activation can partially rescue proteasome dysfunction\u2010mediated cardiac toxicity"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1277-8007","authenticated-orcid":false,"given":"Eleni\u2010Dimitra","family":"Papanagnou","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Biophysics, Faculty of Biology National and Kapodistrian University of Athens  Athens 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