GRAF1 Regulates MYO6 Dependent Mitochondrial Actin Remodeling

Cardiomyocytes are long lived cells that require a constant supply of ATP generated by mitochondria. Mitochondrial dysfunction results in various diseases, highlighting the importance of mitochondrial quality control. Here we demonstrate that GRAF1 regulates mitochondrial quality via interaction with MYO6, a known regulator of mitophagy. Recent studies revealed MYO6 promotes the formation of actin “cages” around damaged mitochondria in response to stress. We show GRAF1 and MYO6 co-localize to depolarized mitochondria. Additionally, we reveal GRAF1 and MYO6 interact and is dependent upon actin polymerization. Knockdown of GRAF1 results in clustered mitochondrial network morphology following mitochondrial depolarization and subsequent recovery. Furthermore, we observe a lack of MYO6 dissociation from mitochondria following knockdown of GRAF1. In addition, GRAF1 was found to promote mitochondrial function in growth conditions requiring mitochondrial dependent oxidative phosphorylation. Our novel findings suggest that GRAF1 regulates the dissociation of actin cages around damaged mitochondria to promote their eventual degradation.Master of Scienc