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Updated: May 13, 2026

Inner Mitochondrial Membrane Sensitivity to Na+ Reveals Partially Segmented Functional CoQ Pools
Published on: July 20, 2022
Effects of alkyl side chain modification of coenzyme Q10 on mitochondrial respiratory chain function and
David M Fash1, Omar M Khdour1, Sunil J Sahdeo2
1Center for BioEnergetics, Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
Abstract:
The effect of the alkyl side chain length of coenzyme Q10 on mitochondrial respiratory chain function has been investigated by the use of synthetic ubiquinone derivatives. Three analogues (3, 4 and 6) were identified that exhibited significantly improved effects on mitochondrial oxygen consumption and mitochondrial membrane potential, and also conferred significant cytoprotection on cultured mammalian cells in which glutathione had been depleted by treatment with diethyl maleate. The analogues also exhibited lesser inhibition of the electron transport chain than idebenone. The results obtained provide guidance for the design of CoQ10 analogues with improved activity compared to that of idebenone (1), the latter of which is undergoing evaluation in the clinic as a therapeutic agent.
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