FYCO1 Regulates Cardiomyocyte Autophagy and Prevents Heart Failure Due to Pressure Overload In Vivo
Christian Kühn, Maja Menke, Frauke Senger, Claudia Mäck, Franziska Dierck, Susanne Hille, Inga Schmidt, Gabriele Brunke, Pia Bünger, Nesrin Schmiedel, Rainer Will, Samuel Sossalla, Derk Frank, Thomas Eschenhagen, Lucie Carrier, Renate Lüllmann‐Rauch, Ashraf Yusuf Rangrez, Norbert Frey
Abstract
Autophagy is a cellular degradation process that has been implicated in diverse disease processes. The authors provide evidence that FYCO1, a component of the autophagic machinery, is essential for adaptation to cardiac stress. Although the absence of FYCO1 does not affect basal autophagy in isolated cardiomyocytes, it abolishes induction of autophagy after glucose deprivation. Likewise, Fyco1-deficient mice subjected to starvation or pressure overload are unable to respond with induction of autophagy and develop impaired cardiac function. FYCO1 overexpression leads to induction of autophagy in isolated cardiomyocytes and transgenic mouse hearts, thereby rescuing cardiac dysfunction in response to biomechanical stress.