Abstract
Autophagy, literally meaning self-eating, is a highly evolutionary conserved process in eukaryotes where elements of the cytoplasm (organelles, macromolecules) are degraded by lysosomes. Autophagy can occur randomly in the cytoplasm or can be selective of a specific organelle. Among other, the specific degradation of mitochondria is called mitophagy. Autophagy and mitophagy have been implicated in several physiopathologies such as neurodegenerative diseases or cancer. Deregulations of autophagy/mitophagy may profoundly affect homeostasis.The aim of my thesis is to characterize the role of the co-chaperonne protein BAG6 in the regulation of mitophagy.BAG6 is a 150kDa protein, also known as BAT3 or Scythe, which functions in the quality control of the cytoplasm. Moreover BAG6 is also involved in immunity, apoptosis or autophagy. Our work showed that it is implicated in the regulation of mitochondrial morphology by inducing mitochondrial fission. Also, BAG6 induces mitophagy: in presence of BAG6, mitophagy markers such as PINK1 and PARKIN are more localized at the mitochondria whereas the expression of mitochondrial specific protein’s (TOM20, TFAM and TIM23) decreases. After its sequence analysis, we discovered that BAG6 is composed of many domains such as the UBL domains and two LIR domains (LC3- Interacting Region) and that BAG6 interacts with LC3 through its LIR2 domain. These features lead to identify BAG6 as a new potential receptor of mitophagy.