%0 Journal Article
%A Toyoda, Yusuke
%A Erkut, Cihan
%A Pan-Montojo, Francisco
%A Boland, Sebastian
%A Stewart, Martin P
%A Müller, Daniel J
%A Wurst, Wolfgang
%A Hyman, Anthony A
%A Kurzchalia, Teymuras V
%T Products of the Parkinson's disease-related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival.
%J Biology open
%V 3
%N 8
%@ 2046-6390
%C Cambridge
%I Company
%M DZNE-2020-04063
%P 777-784
%D 2014
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:25063200
%2 pmc:PMC4133730
%R 10.1242/bio.20149399
%U https://pub.dzne.de/record/137741