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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: MPI-CBG Publications 2014 (arch)     Display Documents



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ID: 705680.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2014 (arch)
Products of the Parkinson's disease-related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival.
Authors:Toyoda, Yusuke; Erkut, Cihan; Pan-Montojo, Francisco; Boland, Sebastian; Stewart, Martin P; Müller, Daniel J.; Wurst, Wolfgang; Hyman, Anthony; Kurzchalia, Teymuras V.
Date of Publication (YYYY-MM-DD):2014
Title of Journal:Biology Open
Volume:3
Issue / Number:8
Start Page:777
End Page:784
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description: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.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:thuem
Affiliations:MPI für molekulare Zellbiologie und Genetik
Identifiers:LOCALID:5836
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