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

• Published in: Biology open Vol. 3; no. 8; pp. 777 - 784
• Main Authors: Toyoda, Yusuke, Erkut, Cihan, Pan-Montojo, Francisco, Boland, Sebastian, Stewart, Martin P., Müller, Daniel J., Wurst, Wolfgang, Hyman, Anthony A., Kurzchalia, Teymuras V.
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists 15.08.2014
• Subjects: Aldehydes; Cellular stress response; D-lactate; Dopamine receptors; Glycolate; Glycolic acid; Glyoxalase; Lactic acid; Membrane potential; Membranes; Mitochondria; Mitochondrial membrane potential; Movement disorders; Neurodegenerative diseases; Neurons; Paraquat; PARK7 protein; Parkinson's disease; Substantia nigra; Survival; Toxins; D-lactate; Parkinson's disease; Glycolate; Glyoxalase; Mitochondrial membrane potential
• ISSN: 2046-6390; 2046-6390
• DOI: 10.1242/bio.20149399

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.