Komlodi 2017 Neuropharmacology

Has title::Komlódi T, Tretter L (2017) Methylene blue stimulates substrate-level phosphorylation catalysed by succinyl-CoA ligase in the citric acid cycle. Neuropharmacology 123:287-98.

» [[Has info::PMID: 28495375]]

Was written by::Komlodi T, Was written by::Tretter L (Was published in year::2017) Was published in journal::Neuropharmacology

Abstract: [[has 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 (forming succinyl-CoA). MB efficiently stimulated SLP and restored the membrane potential in mitochondria also with the combined inhibition of Complex I and ATP synthase. ATP formed by SLP alleviated the energetic insufficiency generated by the lack of oxidative phosphorylation. Thus, the MB-mediated stimulation of SLP might be important in maintaining the energetic competence of mitochondria and in preventing the mitochondrial hydrolysis of glycolytic ATP. The mitochondrial effects of MB are explained by the ability to accept electrons from reducing equivalents and transfer them to cytochrome c bypassing the respiratory Complexes I and III.

Copyright © 2017 Elsevier Ltd. All rights reserved.]] • Keywords: has publicationkeywords::Carbonylcyanide-p-triflouromethoxy-phenylhydrazone (PubChem CID: 3330), has publicationkeywords::Carboxyatractilozide (PubChem CID: 101834999), has publicationkeywords::Citric acid cycle; Malate (PubChem CID: 222656), has publicationkeywords::Methylene blue, has publicationkeywords::Methylene blue (PubChem CID: 6099), has publicationkeywords::Mitochondria, has publicationkeywords::Neurodegeneration, has publicationkeywords::Neuroprotection, has publicationkeywords::Oligomycin (PubChem CID: 78358496), has publicationkeywords::P(1), has publicationkeywords::P(5)-di(adenosine-5′) pentaphosphate (PubChem CID: 6419779), has publicationkeywords::Substrate-level phosphorylation, has publicationkeywords::Succinate (PubChem CID: 1110), has publicationkeywords::α-ketoglutarate (PubChem CID: 51) • Bioblast editor: [[has editor::Kandolf G]], [[has editor::Komlodi T]] • O2k-Network Lab: Was published by MiPNetLab::HU Budapest Tretter L

Labels: MiParea: MiP area::Respiration, MiP area::Pharmacology;toxicology  Pathology: Diseases::Neurodegenerative 

Organism: Organism::Guinea pig  Tissue;cell: tissue and cell::Nervous system  Preparation: Preparation::Isolated mitochondria 

Regulation: Topic::ATP production  Coupling state: Coupling states::LEAK, Coupling states::OXPHOS, Coupling states::ET  Pathway: Pathways::N, Pathways::S  HRR: Instrument and method::Oxygraph-2k