Mitochondrial damage in a Takotsubo syndrome-like mouse model mediated by activation of β-adrenoceptor-Hippo signaling pathway
Wei Wu, Qun Lu, Shan Ma, Jin-Chan Du, Kevin Huynh, Thy Duong, Zhang-Da Pang, D. Donner, Peter J. Meikle, Xiu‐Ling Deng, Xiao‐Jun Du
Abstract
Takotsubo syndrome (TTS) is featured by activation of sympatho-β-adrenoceptor (βAR) system leading to acute loss of ventricular contractile performance. However, the molecular mechanism remains undefined. We demonstrated, in an isoproterenol-induced murine TTS-like model, extensive mitochondrial damage, metabolic dysfunction, and downregulated mitochondrial marker proteins, changes temporarily associated with cardiac dysfunction. Mechanistically, stimulation of βAR activated Hippo signaling pathway and genetic inactivation of Mst1 kinase ameliorated mitochondrial damage and metabolic dysfunction at the acute phase of TTS.