Induction of mitochondrial permeability transition by auranofin, a gold(I)-phosphine derivative.

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Citation

Rigobello MP, Scutari G, Boscolo R, Bindoli A

Induction of mitochondrial permeability transition by auranofin, a gold(I)-phosphine derivative.

Br J Pharmacol. 2002 Aug;136(8):1162-8.

PubMed ID
12163349 [ View in PubMed
]
Abstract

1 Gold(I)-thiolate drugs are compounds that specifically interact with thiol and/or selenol groups and are essentially utilized in the treatment of rheumatoid arthritis. 2 Considering the importance of thiol groups in regulating mitochondrial membrane permeability, the effects of auranofin (S-triethylphosphinegold(I)-2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranoside) , a second-generation gold drug, were studied on mitochondria isolated from rat liver. 3 Auranofin, at submicromolar concentrations, was able to induce the mitochondrial membrane permeability transition observed as swelling and loss of membrane potential. Both events are completely inhibited by cyclosporin A, the specific inhibitor of mitochondrial permeability transition. Calcium ions and energization by succinate are required for the occurrence of permeability transition. 4 By interacting with the active site selenol group, auranofin results as an extremely potent inhibitor of mitochondrial thioredoxin reductase, both isolated and in its mitochondrial environment. 5 It is concluded that auranofin, in the presence of calcium ions, is a highly efficient inducer of mitochondrial membrane permeability transition, potentially referable to its inhibition of mitochondrial thioredoxin reductase.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
AuranofinPeroxiredoxin-5, mitochondrialProteinHumans
Yes
Inhibitor
Details