Abstract 15786: Ddit4L: A Novel Differential Regulator of mTor and Autophagy in Cardiomyocytes

DNA-Damage-Inducible Transcript 4-Like (DDiT4L) protein regulates mTOR signaling in skeletal muscle, however its role in the heart is unknown. Here we investigated the role of DDiT4L in regulating mTOR signaling in cardiomyocytes. We show that DDiT4L differentially regulates mTORC1 and mTORC2 signaling in cardiomyocytes and regulates autophagy in an mTOR dependent, TSC2 independent manner. We studied DDiT4L regulation in the heart using murine models of cardiomyopathy and isolated rat neonatal cardiomyocytes (NRVMs). The functional role of DDiT4L was assessed with loss and gain of function approaches in NRVMs, and an HA-DDiT4L cardiac specific conditional transgenic mouse using Western blotting, PCR, ECHO and confocal imaging. DDiT4L expression increased in mouse models of pathological (pressure overload hypertrophy and dilated cardiomyopathy (myosin heavy chain F764L knock in) n=3-5, p<0.001) but not physiological hypertrophy (swim model) compared to WT. In NRVMs, DDiT4L mRNA increased with the pathologi...