LATS2 promotes cardiomyocyte H9C2 cells apoptosis via the Prx3-Mfn2-mitophagy pathways.

The pathogenesis of cardiomyocyte death is closely associated with mitochondrial homeostasis poorly understood mechanisms. The aim of our study is to explore the contribution of large tumor suppressor kinase 2 (LATS2) to the apoptosis of cardiomyocyte H9C2 cells. Adenovirus-mediated LATS2 overexpression was carried out in H9C2 cells. The cell viability and apoptosis rate were measured an MTT assay, TUNEL staining, western blotting, an ELISA, and an LDH release assay. Mitophagy was quantified using immunofluorescence and western blotting. The overexpression of LATS2 in H9C2 cells drastically promoted cell death. Molecular investigations showed that LATS2 overexpression was associated with mitochondrial injury, as evidenced by increased mitochondrial ROS production, reduced antioxidant factor levels, increased cyt-c liberation into the nucleus and activated mitochondrial caspase-9-dependent apoptotic pathway activity. Furthermore, our results demonstrated that LATS2-mediated mitochondrial malfunction by repressing mitophagy and that the reactivation of mitophagy could sustain mitochondrial integrity and homeostasis in response to LATS2 overexpression. Furthermore, we found that LATS2 inhibited mitophagy by inactivating the Prx3-Mfn2 axis. The reactivation of Prx3-Mfn2 pathways abrogated the LATS2-mediated inhibition of mitochondrial apoptosis in H9C2 cells. The overexpression of LATS2 induces mitochondrial stress by repressing protective mitophagy in a manner dependent on Prx3-Mfn2 pathways, thus reducing the survival of H9C2 cells.