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.
↵§ These authors contributed equally to this work
Author Contributions Y.T., C.E., F.P.-M., D.J.M., A.A.H. and T.V.K. conceived and designed the experiments. Y.T., C.E., F.P.-M., S.B. and M.P.S. performed the experiments. Y.T., C.E., F.P.-M., W.W., A.A.H. and T.V.K. interpreted and analyzed the data. Y.T., C.E., F.P.-M., A.A.H. and T.V.K. wrote the paper.
Competing interests The authors have no competing interests to declare.
- Received July 4, 2014.
- Accepted July 10, 2014.
- © 2014. Published by The Company of Biologists Ltd
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