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PINK1 Phosphorylates Drp1(S616) to Improve Mitochondrial Fission and Inhibit the Progression of Hypertension-Induced HFpEF

(1) Background: Heart failure with preserved ejection fraction (HFpEF) is a major subtype of HF with no effective treatments. Mitochondrial dysfunctions relevant to the imbalance of fusion and fission occur in HFpEF. Drp1 is a key protein regulating mitochondrial fission, and PINK1 is the upstream a...

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Detalles Bibliográficos
Autores principales: Shou, Jian, Huo, Yunlong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570161/
https://www.ncbi.nlm.nih.gov/pubmed/36233236
http://dx.doi.org/10.3390/ijms231911934
Descripción
Sumario:(1) Background: Heart failure with preserved ejection fraction (HFpEF) is a major subtype of HF with no effective treatments. Mitochondrial dysfunctions relevant to the imbalance of fusion and fission occur in HFpEF. Drp1 is a key protein regulating mitochondrial fission, and PINK1 is the upstream activator of Drp1, but their relationship with HF has not been clarified. The aim of the study is to investigate molecular mechanisms of mitochondrial dysfunctions in animals with hypertension-induced HFpEF. (2) Methods and Results: The hypertension-induced HFpEF model was established by feeding Dahl/SS rats with high salt, showing risk factors such as hypertension, mitochondrial dysfunctions, and so on. Physiological and biological measurements showed a decrease in the expression of mitochondrial function-related genes, ATP production, and mitochondrial fission index. PINK1 knockout in H9C2 cardiomyocytes showed similar effects. Moreover, PINK1 myocardium-specific overexpression activated Drp1(S616) phosphorylation and enhanced mitochondrial fission to slow the progression of hypertension-induced HFpEF. (3) Conclusions: PINK1 could phosphorylate Drp1S616 to improve mitochondrial fission and relieve mitochondrial dysfunctions, which highlights potential treatments of HFpEF.