Uloga receptora autofagije u selektivnom uklanjanju mitohondrija

The role of autophagy receptors in selective removal of mitochondria

Autophagy is cellular degradation pathway essential for cell survival, development and differentiation. Its digestive property has been shown important in different pathologies including cancer, neurodegeneration and pathogen removal. Discoveries of specific autophagy receptors have opened a new chapter in the autophagy field. Of great interest is the removal of damaged or excess mitochondria through specialized autophagy- mitophagy. Together with colleagues, I have identified and characterized mitochondrial proteins Nix/Bnip3L and Bnip3 as a mitophagy receptors for recruiting the autophagic machinery to damaged mitochondria and help their elimination (Novak et al, 2010; Zhu et al, 2013). We demonstrated that receptors mediate mitochondrial clearance during reticulocyte differentiation. Our goal is to further study autophagy receptors and proteins associated with mitochondrial clearance to better understand the role of mitophagy and its mechanism. We will study: (1) phosphorylation and dimerization of receptors and the consequences of this events on mitophagy progression; (2)factors that regulate tight connection of apoptosis and mitophagy; (3)potential interplay between mitophagy receptors and other mitophagy-related proteins, like E3-ligase Parkin and kinase PINK1; (4)the effects of mitophagy on cancer development. To reach our goals we will use established methodology in our laboratories including protein identification and interaction techniques (Western blot, IP, GST-pull down, RNAi), immunofluorescent microscopy, mass spectrometry, ITC and NMR. All experiments will be performed using cultured cells. This project proposal has a high capacity to generate very interesting data with high possibility for publications in top scientific journals. Fundamentally, generated data will help to understand the physiological and pathological conditions, such as neurodegeneration and cancer and allow us to manipulate mitophagy to fight diseases.