biostudies-literatureLjubojevic-Holzer SBioTechMed-Graz [Young Researcher GroupsAustrian Science Fund FWFMedical University of Graz scholarshipEuropean Society of Cardiology and Austrian Society of Cardiology1492-1505https://www.ebi.ac.uk/biostudies/studies/S-EPMC9074988biostudies-literatureUnknown118(6)<h4>Aims</h4>Autophagy protects against the development of cardiac hypertrophy and failure. While aberrant Ca2+ handling promotes myocardial remodelling and contributes to contractile dysfunction, the role of autophagy in maintaining Ca2+ homeostasis remains elusive. Here, we examined whether Atg5 deficiency-mediated autophagy promotes early changes in subcellular Ca2+ handling in ventricular cardiomyocytes, and whether those alterations associate with compromised cardiac reserve capacity, which commonly precedes the onset of heart failure.<h4>Methods and results</h4>RT-qPCR and immunoblotting demonstrated reduced Atg5 gene and protein expression and decreased abundancy of autophagy markers in hypertrophied and failing human hearts. The function of ATG5 was examined using cardiomyocyte-speCardiovascular researchLoss of autophagy protein ATG5 impairs cardiac capacity in mice and humans through diminishing mitochondrial abundance and disrupting Ca2+ cycling.PMC9074988V 530P27637-B28I3301-MINOTAURKling KMvon Lewinski DSedej SNickel AKohlhaas MLjubojevic-Holzer SHerbst VAbdellatif MZirlik AMuhlfeld CSchmidt MMaack CKraler SDjalinac NSchipke JScherr DVoglhuber JFranke GTRainer PPfalseLoss of autophagy protein ATG5 impairs cardiac capacity in mice and humans through diminishing mitochondrial abundance and disrupting Ca2+ cycling.<h4>Aims</h4>Autophagy protects against the development of cardiac hypertrophy and failure. While aberrant Ca2+ handling promotes myocardial remodelling and contributes to contractile dysfunction, the role of autophagy in maintaining Ca2+ homeostasis remains elusive. Here, we examined whether Atg5 deficiency-mediated autophagy promotes early changes in subcellular Ca2+ handling in ventricular cardiomyocytes, and whether those alterations associate with compromised cardiac reserve capacity, which commonly precedes the onset of heart failure.<h4>Methods and results</h4>RT-qPCR and immunoblotting demonstrated reduced Atg5 gene and protein expression and decreased abundancy of autophagy markers in hypertrophied and failing human hearts. The function of ATG5 was examined using cardiomyocyte-spe2022-01-01T00:00:00Z2022 May2025-04-03T22:22:26.094Z2024-12-03T23:39:17.808ZS-EPMC90749883375224210.1093/cvr/cvab112