Cytochrome bc1 regulates the mitochondrial permeability transition by two distinct pathways

Armstrong, Jeffrey, Yang, Hongyuan, Duan, Wei and Whiteman, Matthew 2004, Cytochrome bc1 regulates the mitochondrial permeability transition by two distinct pathways, Journal of biological chemistry, vol. 279, no. 48, pp. 50420-50428.

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Title Cytochrome bc1 regulates the mitochondrial permeability transition by two distinct pathways
Author(s) Armstrong, Jeffrey
Yang, Hongyuan
Duan, Wei
Whiteman, Matthew
Journal name Journal of biological chemistry
Volume number 279
Issue number 48
Start page 50420
End page 50428
Publisher American Society for Biochemistry and Molecular Biology
Place of publication Bethesda, Md.
Publication date 2004-11-26
ISSN 0021-9258
1083-351X
Summary The 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.
Language eng
Field of Research 110199 Medical Biochemistry and Metabolomics not elsewhere classified
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2004, The American Society for Biochemistry and Molecular Biology, Inc.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30009148

Document type: Journal Article
Collection: School of Medicine
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