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

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Metallomics Vol - 6 Issue - 9

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

Content Provider	Royal Society of Chemistry (RSC)
Author	McEwan, Alastair G. Donnelly, Paul S. Djoko, Karrera Y.
Copyright Year	2014
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.
Starting Page	2250
Ending Page	2259
Page Count	10
File Format	HTM / HTML PDF
ISSN	17565901
Volume Number	6
Issue Number	12
Journal	Metallomics
DOI	10.1039/c4mt00226a
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Electron transport chain Cu NADH Coenzyme Q10 Cellular respiration Nicotinamide adenine dinucleotide NADH dehydrogenase Enzyme inhibitor Ion Semicarbazone Ionophore Copper
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

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