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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: | Other health not elsewhere classified |
| UTAS Author: | Guven, N (Dr Nuri Guven) |
| ID Code: | 79262 |
| Year Published: | 2012 |
| Web of Science® Times Cited: | 59 |
| Deposited By: | Pharmacy |
| Deposited On: | 2012-08-29 |
| Last Modified: | 2017-11-02 |
| Downloads: | 383 View Download Statistics |
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