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Features of idebenone and related short-chain quinones that rescue ATP levels under conditions of impaired mitochondrial complex I

Citation

Erb, M and Hoffmann-Enger, B and Deppe, H and Soedberdt, M and Haefeli, RH and Rummey, C and Feurer, A and Guven, N, Features of idebenone and related short-chain quinones that rescue ATP levels under conditions of impaired mitochondrial complex I, PLoS One, 7, (4) Article e36153. ISSN 1932-6203 (2012) [Refereed Article]


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DOI: doi:10.1371/journal.pone.0036153

Abstract

Short-chain quinones have been investigated as therapeutic molecules due to their ability to modulate cellular redox reactions, mitochondrial electron transfer and oxidative stress, which are pathologically altered in many mitochondrial and neuromuscular disorders. Recently, we and others described that certain short-chain quinones are able to bypass a deficiency in complex I by shuttling electrons directly from the cytoplasm to complex III of the mitochondrial respiratory chain to produce ATP. Although this energy rescue activity is highly interesting for the therapy of disorders associated with complex I dysfunction, no structure-activity-relationship has been reported for short-chain quinones so far. Using a panel of 70 quinones, we observed that the capacity for this cellular energy rescue as well as their effect on lipid peroxidation was influenced more by the physicochemical properties (in particular logD) of the whole molecule than the quinone moiety itself. Thus, the observed correlations allow us to explain the differential biological activities and therapeutic potential of short-chain quinones for the therapy of disorders associated with mitochondrial complex I dysfunction and/or oxidative stress.

Item Details

Item Type:Refereed Article
Keywords:pharmaceutical drug development
Research Division:Chemical Sciences
Research Group:Medicinal and Biomolecular Chemistry
Research Field:Medicinal and Biomolecular Chemistry not elsewhere classified
Objective Division:Health
Objective Group:Other Health
Objective Field:Health not elsewhere classified
Author:Guven, N (Dr Nuri Guven)
ID Code:79262
Year Published:2012
Web of Science® Times Cited:26
Deposited By:Pharmacy
Deposited On:2012-08-29
Last Modified:2017-11-02
Downloads:249 View Download Statistics

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