Role of chaperones in selective autophagy of protein inclusions

Autophagy is a catabolic process that facilitates degradation of intracellular components in lysosomes[1] (Fig. 1). Up-regulation of autophagy to clear protein inclusions has been shown to alleviate pathogenesis of various neurodegenerative diseases and represents an attractive therapeutic approach to slow down disease progression[1-2]. However, we have found that autophagic clearance of disease-linked inclusions is not a universal phenomenon and, instead, cells target the removal of these protein inclusions in a selective manner[3] (Fig. 1). Currently, the factor(s) governing selection of protein inclusions for autophagic degradation is not well understood. Chaperones and co-chaperones, which modulate protein quality control, have recently been suggested to be critical in this selection process[4]. In this study, we seek to investigate whether the association of pertinent chaperone(s) with protein inclusions determines the susceptibility of protein inclusions toward autophagic degradation. [3rd Award