Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 234, Issue 7, Pages 11835-11841Publisher
WILEY
DOI: 10.1002/jcp.27892
Keywords
Mitochondrial quality control; mitophagy; myocardial protection; Notch1
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Funding
- National Natural Science Foundation of China [81260024, 81460065, 81860054, 81570262, 81860045]
- Natural Science Foundation of Jiangxi Province [20152ACB20026]
- Jiangxi Provincial Universities Science Technology Floor Plan [KJLD1401]
- Gan Po Talent 555 Program
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Mitochondrial quality control is a new target for myocardial protection. Notch signaling plays an important role in heart development, maturation, and repair. However, the role of Notch in the myocardial mitochondrial quality control remains elusive. In this study, we isolated myocardial cells from rats and established myocardial ischemia reperfusion injury (IRI) model. We modulated Notch1 expression level in myocardial cells via infection with recombinant adenoviruses Ad-N1ICD and Ad-shN1ICD. We found that IR reduced myocardial cells viability, but Notch1 overexpression increased the viability of myocardial cells exposed to IRI. In addition, Notch1 overexpression improved ATP production, increased mitochondrial fusion and decreased mitochondrial fission, and inhibited mitophagy in myocardial cells exposed to IRI. However, N1ICD knockdown led to opposite effects. The myocardial protection role of Notch1 was related to the inhibition of Pink1 expression and Mfn2 and Parkin phosphorylation. In conclusion, Notch1 exerts myocardial protection and this is correlated with the maintenance of mitochondrial quality control and the inhibition of Pink1/Mfn2/Parkin signaling.
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