Mst1-mediated phosphorylation of Bcl-xL is required for myocardial reperfusion injury.

摘要: Mst1 is a central Ser-Thr kinase in the Hippo pathway, which promotes apoptosis and inhibits cell proliferation. We have shown previously that, cardiomyocytes, oxidative stress activates at mitochondria, where phosphorylates Bcl-xL Ser14, inducing dissociation of from Bax thereby promoting apoptosis. However, functional significance Ser14 phosphorylation endogenous vivo remains elusive. generated knockin (KI) mice replaced with Ala. KI were born expected Mendelian ratio, adult exhibited normal cardiac morphology function baseline. protected myocardial ischemia/reperfusion (I/R) injury reduced cardiomyocyte Although suppression also I/R injury, there was no additive protective effect when inhibited mice. The development dilated cardiomyopathy induced by cardiac-specific overexpression ameliorated Lats2 YAP, two other key components not affected These results suggest that plays an essential role mediating both acting as downstream mediator independently canonical pathway.