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Cytochrome bc1 regulates the mitochondrial permeability transition by two distinct pathways
journal contribution
posted on 2004-11-26, 00:00 authored by J Armstrong, H Yang, Wei DuanWei Duan, M WhitemanThe mitochondrial permeability transition (MPT) pore is a calcium-sensitive channel in the mitochondrial inner membrane that plays a crucial role in cell death. Here we show that cytochrome bc1 regulates the MPT in isolated rat liver mitochondria and in CEM and HL60 cells by two independent pathways. Glutathione depletion activated the MPT via increased production of reactive oxygen species (ROS) generated by cytochrome bc1. The ROS producing mechanism in cytochrome bc1 involves movement of the "Rieske" iron-sulfur protein subunit of the enzyme complex, because inhibition of cytochrome bc1 by pharmacologically blocking iron-sulfur protein movement completely abolished ROS production, MPT activation, and cell death. The classical inhibitor of the MPT, cyclosporine A, had no protective effect against MPT activation. In contrast, the calcium-activated, cyclosporine A-regulated MPT in rat liver mitochondria was also blocked with inhibitors of cytochrome bc1. These results indicate that electron flux through cytochrome bc1 regulates two distinct pathways to the MPT, one unregulated and involving mitochondrial ROS and the other regulated and activated by calcium.
History
Journal
Journal of biological chemistryVolume
279Issue
48Pagination
50420 - 50428Publisher
American Society for Biochemistry and Molecular BiologyLocation
Bethesda, Md.Publisher DOI
Link to full text
ISSN
0021-9258eISSN
1083-351XLanguage
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2004, The American Society for Biochemistry and Molecular Biology, Inc.Usage metrics
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