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bioRxiv · 10.1101/006916

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

Yusuke Toyoda·Cihan Erkut·Francisco Pan-Montojo·Sebastian Boland·Martin P. Stewart·Daniel J. M?ller·Wolfgang Wurst·Anthony A. Hyman·Teymuras V. Kurzchalia
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Abstract

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.

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Yusuke Toyoda, Cihan Erkut, Francisco Pan-Montojo, Sebastian Boland, Martin P. Stewart, Daniel J. M?ller, Wolfgang Wurst, Anthony A. Hyman, Teymuras V. Kurzchalia. 2014-07-04. Products of the Parkinson’s-disease related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival. https://doi.org/10.1101/006916

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