Exploration of novel model systems to study phosphoglycerate modifications in vivo

Inactivation of the enzyme PARK7/DJ1 is a rare cause for Parkinson’s disease. Previous work in my host laboratory has shown that the PD protein PARK7/DJ-1 prevents the formation of damaged phosphoglycerate-modified proteins and metabolites by hydrolyzing cyclic-1,3-phosphoglycerate, which spontaneously forms from the glycolytic metabolite 1,3-biphosphoglycerate and avidly reacts with amino groups of proteins, thereby modifying them with phosphoglycerate. Curiously, inactivation of PARK7/DJ1 leads not only to the accumulation of phosphoglycerate-modified proteins but also glycerate-modified proteins, suggesting that a phosphatase might act on phosphoglycerate-modified proteins. At present, the relative contribution of phosphoglycerate- and glycerate modified proteins to the development of Parkinson’s disease remains elusive. In the course of my memoire, I wanted to explore whether D. melanogaster and C. elegans could be used to further explore this question. To achieve this, I combined several complementary methods in protein biochemistry, enzymology and mass spectrometry, allowing me to characterize the enzymatic activities of putative orthologs in these organisms. This represents the basis for future explorations in vivo.