Deletion of the E3 ubiquitin ligase, Parkin, exacerbates chronic alcohol intake?induced cardiomyopathy through an Ambra1?dependent mechanism

Background and Purpose Chronic alcohol consumption contributes to contractile dysfunction unfavourable geometric changes in myocardium, accompanied by altered autophagy disturbed mitochondrial homeostasis. The E3 ubiquitin ligase Parkin encoded PARK2 gene maintains a fundamental role regulating mitophagy homeostasis, although little is known of its the aetiology alcoholic cardiomyopathy. Here we assessed effects deletion chronic alcohol-evoked cardiotoxicity. Experimental Approach Following (4%) or control diet intake for 8 weeks, adult male wild-type (WT) knockout (Parkin?/?) mice were examined using echocardiography. Cardiomyocyte mechanical properties, morphology damage also evaluated. Autophagy levels LC3B GFP-LC3 puncta, lysosome-dependent autophagic flux was scrutinized GFP-mRFP-LC3 puncta Bafilomycin A1 treatment. Key Results exposure provoked myocardium led cardiac defects, further exacerbated knockout. PINK1/Parkin-mediated without affecting flux, which diminished deletion. adenovirus infection neonatal rat cardiomyocytes increased protected against alcohol-induced myocardial injury, blocked siRNA Ambra1 (Autophagy Beclin1 regulator 1). Immunofluorescence staining co-immunoprecipitation assays showed interactions between Ambra1. Conclusions Implications essential homeostasis challenge, autophagy/mitophagy maintenance integrity through interaction with