Structure and function of the complex of mitochondrial autophagy receptor protein FUNDC1 and LC3

Alterations in mitophagy are involved in many serious diseases. Mitophagy receptors mediate mitochondrial autophagy through interaction with LC3. FUNDC1 is a novel hypoxia-induced mitophagy receptor which was recently discovered by Dr. Feng Du and his collaborators. However, the 3-D structures of Fundc1 itself and its homologues are unavailabe. Recently, we aquired the crystals of the truncated protein of FUNDC1 with members of LC3 family, and in this project we will further refine the complex crystal and determine its structure. Based on this complex structure, we will then engineer a serials of key mutants to elucidate the mechanism of how the interactions between FUNDC1 and LC3 to regulate the mitophagy using biochemistry and cell biology methods. Our study will provide insights into not only FUNDC1 itself but also FUNDC1 mediated-mitophagy and will be helpful for us to better understand the working mechanism of other mitophagy receptors such as NIX and BNIP3 in mammals and ATG32 in yeast.