The mechanism of 14-3-3η in thyroxine induced mitophagy in cardiomyocytes.

Hyperthyroidism is becoming increasingly important as an independent risk factor for cardiovascular disease, eventually resulting in cardiac hypertrophy and heart failure. The 14-3-3 protein family subtypes regulate many cellular processes in eukaryotes by interacting with a diverse array of client proteins. Considering that the 14-3-3η protein protects cardiomyocytes by affecting mitochondrial function, exploring the biological influence and molecular mechanisms by which 14-3-3η alleviates the cardiac hypertrophy of hyperthyroidism is imperative. In vivo and in vitro, RT-PCR, Western blot, and Mitochondrial tracking assay were performed to understand the molecular mechanism of thyroxine-induced cardiomyocyte hypertrophy. HE staining, transmission electron microscopy, and immunofluorescence were used to observe intuitively changes of hearts and cardiomyocytes. The in vivo and in vitro results indicated that overexpression of the 14-3-3η ameliorated thyroxine-induced cardiomyocyte hypertrophy, whereas knockdown of the 14-3-3η protein aggravated thyroxine-induced cardiomyocyte hypertrophy. Additionally, overexpression of the 14-3-3η protein reduces thyroxine-induced mitochondrial damage and mitophagy in cardiomyocytes. Overexpression of 14-3-3η protein improves excessive mitophagy in the myocardium caused by thyroxine and thus prevents cardiac hypertrophy.