Inhibition of respiratory Complex I by copper(ii)-bis(thiosemicarbazonato) complexes

Djoko, Karrera Y., Donnelly, Paul S. and McEwan, Alastair G. (2014) Inhibition of respiratory Complex I by copper(ii)-bis(thiosemicarbazonato) complexes. Metallomics, 6 12: 2250-2259. doi:10.1039/C4MT00226A

Author Djoko, Karrera Y.
Donnelly, Paul S.
McEwan, Alastair G.
Title Inhibition of respiratory Complex I by copper(ii)-bis(thiosemicarbazonato) complexes
Journal name Metallomics   Check publisher's open access policy
ISSN 1756-5901
Publication date 2014-11
Year available 2014
Sub-type Article (original research)
DOI 10.1039/C4MT00226A
Open Access Status Not Open Access
Volume 6
Issue 12
Start page 2250
End page 2259
Total pages 10
Place of publication Cambridge, United Kingdom
Publisher Royal Society of Chemistry
Collection year 2015
Language eng
Formatted abstract
Several copper(II) complexes of bis(thiosemicarbazones) [Cu(btsc)s] show promise as therapeutics for the treatment of neurological diseases, cancers and bacterial infections. These complexes are thought to act primarily as copper ionophores or “copper boosting” agents, whereby the CuII centre is reduced by cytosolic reductants and CuI is released as “free” or “bioavailable” ion. It is then assumed that the dissociated CuI ion is the species responsible for many of the observed biological effects of Cu(btsc)s. We recently showed that Cu(btsc) complexes inhibited NADH dehydrogenases in the bacterial respiratory chain. In this work, we demonstrate that Cu(btsc) complexes also inhibit mitochondrial respiration and that Complex I in the mitochondrial electron transport chain is a specific target of inhibition. However, bioavailable Cu ions do not appear to contribute to the action of Cu(btsc) as a respiratory inhibitor. Instead, an intact Cu(btsc) molecule may bind reversibly and competitively to the site of ubiquinone binding in Complex I. Our results add to the growing body of evidence that the intact complex may be important in the overall cellular activity of Cu(btsc) complexes and further the understanding of their biological effects as a potential therapeutic.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes epub ahead of print

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
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Created: Fri, 07 Nov 2014, 10:23:29 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences