Products of the Parkinson's disease-related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival

• Main Authors: Yusuke Toyoda, Cihan Erkut, Francisco Pan-Montojo, Sebastian Boland, Martin P. Stewart, Daniel J. Müller, Wolfgang Wurst, Anthony A. Hyman, Teymuras V. Kurzchalia
• Format: Article
• Language: English
• Published: The Company of Biologists 2014-07-01
• Series: Biology Open
• Subjects: Parkinson's disease; Glyoxalase; D-lactate; Glycolate; Mitochondrial membrane potential
• Online Access: http://bio.biologists.org/content/3/8/777

Parkinson's disease is associated with mitochondrial decline in dopaminergic neurons of the substantia nigra. One of the genes linked with the onset of Parkinson's disease, DJ-1/PARK7, 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.