title: Products of the Parkinson's disease-related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival.
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.
authors: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
authors: Yusuke
authors: Y
authors: Toyoda
authors: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
authors: Cihan
authors: C
authors: Erkut
authors: 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.
authors: Francisco
authors: F
authors: Pan-Montojo
authors: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
authors: Sebastian
authors: S
authors: Boland
authors: Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland Present address: Koch Institute at MIT, 500 Main Street, Cambridge, MA 02139, USA.
authors: Martin P
authors: MP
authors: Stewart
authors: Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland.
authors: Daniel J
authors: DJ
authors: Müller
authors: 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.
authors: Wolfgang
authors: W
authors: Wurst
authors: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany hyman@mpi-cbg.de kurzchalia@mpi-cbg.de.
authors: Anthony A
authors: AA
authors: Hyman
authors: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany hyman@mpi-cbg.de kurzchalia@mpi-cbg.de.
authors: Teymuras V
authors: TV
authors: Kurzchalia
keywords: D-lactate; Glycolate; Glyoxalase; Mitochondrial membrane potential; Parkinson's disease