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Toyoda Y, Erkut C, Pan-Montojo F, et al. Products of the Parkinson's disease-related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival. Biol Open. 2014;3(8):777-84doi: 10.1242/bio.20149399.
Toyoda, Y., Erkut, C., Pan-Montojo, F., Boland, S., Stewart, M. P., Müller, D. J., Wurst, W., Hyman, A. A., & Kurzchalia, T. V. (2014). Products of the Parkinson's disease-related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival. Biology open, 3(8), 777-84. https://doi.org/10.1242/bio.20149399
Toyoda, Yusuke, et al. "Products of the Parkinson's disease-related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival." Biology open vol. 3,8 (2014): 777-84. doi: https://doi.org/10.1242/bio.20149399
Toyoda Y, Erkut C, Pan-Montojo F, Boland S, Stewart MP, Müller DJ, Wurst W, Hyman AA, Kurzchalia TV. Products of the Parkinson's disease-related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival. Biol Open. 2014 Jul 25;3(8):777-84. doi: 10.1242/bio.20149399. PMID: 25063200; PMCID: PMC4133730.
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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.

Biology open

Yusuke Toyoda, Cihan Erkut, Francisco Pan-Montojo, Sebastian Boland, Martin P Stewart, Daniel J Müller, Wolfgang Wurst, Anthony A Hyman, Teymuras V Kurzchalia

Affiliations

  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 [email protected] [email protected].

PMID: 25063200 PMCID: PMC4133730 DOI: 10.1242/bio.20149399

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.

© 2014. Published by The Company of Biologists Ltd.

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

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