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Biol Open. 2014 Jul 25;3(8):777-84. doi: 10.1242/bio.20149399.

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

Author information

1
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
2
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany Munich Cluster for Systems Neurology (SyNergy), Adolf Butenandt Institute, Ludwig-Maximilians-Universität München Schillerstrasse 44, 80336 Munich, Germany Present address: Neurologische Klinik und Poliklinik, Klinikum der Universität Muenchen, Marchioninistrasse 15, 81377 Munich, Germany.
3
Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland Present address: Koch Institute at MIT, 500 Main Street, Cambridge, MA 02139, USA.
4
Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland.
5
Technische Universität München-Weihenstephan, c/o Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg/Munich, Germany German Center for Neurodegenerative Diseases (DZNE), Site Munich Schillerstrasse 44, 80336 Munich, Germany Munich Cluster for Systems Neurology (SyNergy), Adolf Butenandt Institute, Ludwig-Maximilians-Universität München Schillerstrasse 44, 80336 Munich, Germany.
6
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany hyman@mpi-cbg.de kurzchalia@mpi-cbg.de.

Abstract

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.

KEYWORDS:

D-lactate; Glycolate; Glyoxalase; Mitochondrial membrane potential; Parkinson's disease

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