Parkin Insufficiency Accentuates High-Fat Diet–Induced Cardiac Remodeling and Contractile Dysfunction Through VDAC1-Mediated Mitochondrial Ca2+ Overload
JACC: Basic to Translational Science, cilt.7, sa.8, ss.779-796, 2022 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 7 Sayı: 8
- Basım Tarihi: 2022
- Doi Numarası: 10.1016/j.jacbts.2022.03.007
- Dergi Adı: JACC: Basic to Translational Science
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, Directory of Open Access Journals
- Sayfa Sayıları: ss.779-796
- Anahtar Kelimeler: Ca2+ overload, heart, high-fat diet, mitochondria, Parkin, VDAC1
- Ankara Yıldırım Beyazıt Üniversitesi Adresli: Evet
Özet
© 2022 The AuthorsMitochondrial Ca2+ 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 Ca2+ 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 Ca2+ uniporter complex. These data suggest that Parkin-mediated proteolysis of VDAC type 1 is a promising therapeutic target for obesity cardiomyopathy.