| First Author | Wu NN | Year | 2022 |
| Journal | JACC Basic Transl Sci | Volume | 7 |
| Issue | 8 | Pages | 779-796 |
| PubMed ID | 36061337 | Mgi Jnum | J:351588 |
| Mgi Id | MGI:7702350 | Doi | 10.1016/j.jacbts.2022.03.007 |
| Citation | Wu NN, et al. (2022) Parkin Insufficiency Accentuates High-Fat Diet-Induced Cardiac Remodeling and Contractile Dysfunction Through VDAC1-Mediated Mitochondrial Ca(2+) Overload. JACC Basic Transl Sci 7(8):779-796 |
| abstractText | Mitochondrial Ca(2+) overload contributes to obesity cardiomyopathy, yet mechanisms that directly regulate it remain elusive. The authors investigated the role of Parkin on obesity-induced cardiac remodeling and dysfunction in human hearts and a mouse model of 24-week high-fat diet (HFD) feeding. Parkin knockout aggravated HFD-induced cardiac remodeling and dysfunction, mitochondrial Ca(2+) overload, and apoptosis without affecting global metabolism, blood pressure, and aortic stiffness. Parkin deficiency unmasked HFD-induced decline in voltage-dependent anion channel (VDAC) type 1 degradation through the ubiquitin-proteasome system but not other VDAC isoforms or mitochondrial Ca(2+) uniporter complex. These data suggest that Parkin-mediated proteolysis of VDAC type 1 is a promising therapeutic target for obesity cardiomyopathy. |
