Methylene blue stimulates substrate-level phosphorylation catalysed by succinyl-CoA ligase in the citric acid cycle

Neuropharmacology
T Komlódi, Laszlo Tretter

Abstract

Methylene blue (MB), a potential neuroprotective agent, is efficient in various neurodegenerative disease models. Beneficial effects of MB have been attributed to improvements in mitochondrial functions. Substrate-level phosphorylation (SLP) results in the production of ATP independent from the ATP synthase (ATP-ase). In energetically compromised mitochondria, ATP produced by SLP can prevent the reversal of the adenine nucleotide translocase and thus the hydrolysis of glycolytic ATP. The aim of the present study was to investigate the effect of MB on mitochondrial SLP catalysed by succinyl-CoA ligase. Measurements were carried out on isolated guinea pig cortical mitochondria respiring on α-ketoglutarate, glutamate, malate or succinate. The mitochondrial functions and parameters like ATP synthesis, oxygen consumption, membrane potential, and NAD(P)H level were followed online, in parallel with the redox state of MB. SLP-mediated ATP synthesis was measured in the presence of inhibitors for ATP-ase and adenylate kinase. In the presence of the ATP-ase inhibitor oligomycin MB stimulated respiration with all of the respiratory substrates. However, the rate of ATP synthesis increased only with substrates α-ketoglutarate and glutamate ...Continue Reading

Citations

Feb 17, 2018·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Philippe HaouziFrederic Bouillaud
Dec 28, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Philippe HaouziAnnick Judenherc-Haouzi
Mar 26, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Philippe HaouziFrederic Bouillaud
May 7, 2020·Annals of the New York Academy of Sciences·Philippe HaouziJoseph Y Cheung
Nov 17, 2020·Toxicology Reports·Philippe HaouziNicole Tubbs
Apr 21, 2018·Dental Materials : Official Publication of the Academy of Dental Materials·Krisztina MikulásLászló Tretter

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