A protein mutated in Parkinson's disease prevents damage of metabolites and proteins caused by a glycolytic metabolite

Abstract

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 discoveredHere 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.