@article {Toyoda006916, author = {Yusuke Toyoda and Cihan Erkut and Francisco Pan-Montojo and Sebastian Boland and Martin P. Stewart and Daniel J. M{\"u}ller and Wolfgang Wurst and Anthony A. Hyman and Teymuras V. Kurzchalia}, title = {Products of the Parkinson{\textquoteright}s-disease related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival}, elocation-id = {006916}, year = {2014}, doi = {10.1101/006916}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Parkinson{\textquoteright}s disease is associated with mitochondrial decline in dopaminergic neurons of the substantia nigra. One of the genes, DJ-1/PARK7, linked with the onset of Parkinson{\textquoteright}s disease, belongs to a novel glyoxalase family and influences mitochondrial activity. It has been assumed that glyoxalases fulfill this task by detoxifying aggressive aldehyde by-products of metabolism. Here we show that supplying either D-lactate or glycolate, products of DJ-1, rescues the requirement for the enzyme in maintenance of mitochondrial potential. We further show that glycolic acid and D-lactic acid can elevate lowered mitochondrial membrane potential caused by silencing PINK-1, another Parkinson{\textquoteright}s related gene, as well as by paraquat, an environmental toxin known to be linked with Parkinson{\textquoteright}s disease. We propose that DJ-1 and consequently its products are components of a novel pathway that stabilizes mitochondria during cellular stress. We go on to show that survival of cultured mesencephalic dopaminergic neurons, defective in Parkinson{\textquoteright}s disease, is enhanced by glycolate and D-lactate. Because glycolic and D-lactic acids occur naturally, they are therefore a potential therapeutic route for treatment or prevention of Parkinson{\textquoteright}s disease.}, URL = {https://www.biorxiv.org/content/early/2014/07/04/006916}, eprint = {https://www.biorxiv.org/content/early/2014/07/04/006916.full.pdf}, journal = {bioRxiv} }