(672.2) A protein mutated in Parkinsons disease prevents damage of metabolites and proteins caused by a glycolytic metabolite

Poster Board Number: A386

Isaac Heremans (Université Catholique de Louvain - de Duve Institute amp; WELBIO), Francesco Caligiore (Université Catholique de Louvain - de Duve Institute amp; WELBIO), Isabelle Gerin (Université Catholique de Louvain - de Duve Institute amp; WELBIO), Marina Bury (Université Catholique de Louvain - de Duve Institute amp; WELBIO), Marilena Lutz (German Cancer Research Center (DKFZ) - Division of Signal Transduction in Cancer and Metabolism), Julie Graff (Université Catholique de Louvain - de Duve Institute amp; WELBIO), Vincent Stroobant (Ludwig Institute), Didier Vertommen (Université Catholique de Louvain - de Duve Institute, PHOS unit and MASSPROT platform), Aurelio Teleman (German Cancer Research Center (DKFZ) - Division of Signal Transduction in Cancer and Metabolism), Emile Van Schaftingen (Université Catholique de Louvain - de Duve Institute amp; WELBIO), Guido Bommer (Université Catholique de Louvain - de Duve Institute amp; WELBIO)

The accumulation of cellular damage  is suspected to contribute to aging and neurodegenerative diseases. Oxidative stress and environmental factors likely play a role, but other damaging agents likely remain to be discovered

Here we report that an enzyme mutated in hereditary Parkinson’s disease achieves the seemingly impossible task to prevent damage caused by a glycolytic metabolite without affecting the metabolite itself. Inactivation of this enzyme in model systems ranging from flies to human cells leads to the accumulation of a wide range of metabolites and proteins damaged by a newly discovered covalent modification.

Thus, this enzyme represents a highly conserved strategy to prevent damage in cells that perform glycolysis. Thereby, it interrupts a fundamental link between carbohydrate metabolism and a type of cellular damage that might contribute to the development of Parkinson’s disease.

This project has received funding from WELBIO grants (to E.V.S. and G.T.B.), the European Research Council (ERC) under the European Unionamp;rsquo;s Horizon 2020 research and innovation programme (Grant agreement No. 771704, to G.T.B.), the Fondation Contre le Cancer (to G.T.B.), a FRIA fellowship (to I.P.H.), a TELEVIE fellowship (to M.B.), an Incentive grant of the FNRS (to G.T.B), the DFG SFB1118 grant to A.A.T., as well as support from the Universitamp;eacute; catholique de Louvain and from the Fonds Maurange.