Abstract
Autophagy is a process of self-digestion of intracellular material based on the formation of double membrane vesicles called autophagosomes that sequester organelles and macromolecules and then fuse with lysosomes to allow their degradation.The selective degradation of mitochondria by autophagy is named mitophagy. By eliminating superfluous or damaged mitochondria, that cause toxic and mutagenic oxidative stress, mitophagy contributes to the maintenance of cellular homeostasis. Its regulation involves signaling pathways such as the PINK1-PARKIN pathway and specific receptors called mitophagy receptors.The BAG6 protein is a co-chaperon of HSP70 and has a variety of functions such as regulation of apoptosis, epigenetic modifications, protein folding, and peptide removal by the ubiquitin-proteasome system. BAG6 is also essential for autophagy by regulating the intracellular localization of EP300 acetyltransferase responsible for ATGs protein acetylation.In this thesis, we showed that BAG6 is located in the mitochondria. More precisely, BAG6 is located in the mitochondrial matrix under basal conditions and then relocalizes in the outer membrane when the mitochondria are depolarized. In parallel, BAG6 promotes the recruitment of the mitochondrial fission complex DRP1 and the proteins PINK1 and PARKIN involved in mitophagic signalling, which gives it a pro-mitophagic effect. Finally, BAG6 also interacts with LC3 via a LIR domain (LC3 Interacting Region) and its effect on mitophagy depends on this interaction, making BAG6 a putative mitophagy receptor.