A model naphthenic acid decouples oxidative phosphorylation through selective inhibition of mitochondrial complex activity.

Autor: Kalvani Z; Atlantic Veterinary College, Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, Canada. Electronic address: Zkalvani@upei.ca., Kamunde C; Atlantic Veterinary College, Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, Canada., Stevens D; Atlantic Veterinary College, Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, Canada., van den Heuvel MR; Atlantic Veterinary College, Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, Canada; Canadian Rivers Institute, Department of Biology, University of Prince Edward Island,Charlottetown,Canada.
Jazyk: angličtina
Zdroj: Environmental toxicology and pharmacology [Environ Toxicol Pharmacol] 2024 Apr; Vol. 107, pp. 104386. Date of Electronic Publication: 2024 Feb 09.
DOI: 10.1016/j.etap.2024.104386
Abstrakt: The naphthenic acid fraction compound (NAFC), 3,5-dimethyladamantane-1-acetic acid, was tested for its ability to uncouple mitochondrial oxidative phosphorylation. Mitochondria isolated from rainbow trout (Oncorhynchus mykiss) liver were exposed to 3,5-dimethyladamantane-1-acetic acid in state 3 and 4 respiration, and mitochondrial membrane potential were quantified. Electron transport chain (ETC) protein complexes were isolated using pharmacological agents and inhibitors, and their activities measured. The NAFC compound completely inhibited states 3 and 4 respiration with an IC50 of 0.77 and 1.01 mM, respectively. The NAFC compound partially uncoupled mitochondrial membrane potential in state 3 and 4 respiration with an IC50 of 2.19 and 1.73 mM, respectively. The NAFC impaired the activities of ETC protein complexes with a 9.5-fold range in sensitivity. The relative inhibitory effect of the ETC protein complexes to NAFC was CIV≥CI>CIII>CII. The impairment of mitochondrial oxidative phosphorylation by adamantane 3,5-dimethyladamantane-1-acetic acid is mediated via its inhibition of ETC protein complexes.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michael van den Heuvel reports financial support and administrative support were provided by Natural Sciences and Engineering Research Council of Canada. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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