PT - JOURNAL ARTICLE AU - Yusuke Toyoda AU - Cihan Erkut AU - Francisco Pan-Montojo AU - Sebastian Boland AU - Martin P. Stewart AU - Daniel J. Müller AU - Wolfgang Wurst AU - Anthony A. Hyman AU - Teymuras V. Kurzchalia TI - Products of the Parkinson’s-disease related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival AID - 10.1101/006916 DP - 2014 Jan 01 TA - bioRxiv PG - 006916 4099 - http://biorxiv.org/content/early/2014/07/04/006916.short 4100 - http://biorxiv.org/content/early/2014/07/04/006916.full AB - Parkinson’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’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’s related gene, as well as by paraquat, an environmental toxin known to be linked with Parkinson’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’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’s disease.