Premium
Induction of mitochondrial permeability transition by auranofin, a Gold(I)‐phosphine derivative
Author(s) -
Rigobello Maria Pia,
Scutari Guido,
Boscolo Rita,
Bindoli Alberto
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704823
Subject(s) - auranofin , mitochondrial permeability transition pore , thioredoxin reductase , voltage dependent anion channel , chemistry , membrane permeability , mitochondrion , inner mitochondrial membrane , biochemistry , thioredoxin , mitochondrial membrane transport protein , biophysics , pharmacology , bacterial outer membrane , oxidative stress , biology , membrane , apoptosis , programmed cell death , immunology , rheumatoid arthritis , escherichia coli , gene
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. 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‐β‐ D ‐glucopyranoside), a second‐generation gold drug, were studied on mitochondria isolated from rat liver. 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. 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. 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.British Journal of Pharmacology (2002) 136 , 1162–1168. doi: 10.1038/sj.bjp.0704823