Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 491, Issue 1-2, Pages 39-45Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2009.09.002
Keywords
Cyclophilin; Oxidative stress; Mitochondria; Redox sensor
Categories
Funding
- Fonds pour la formation a la Recherche clans l'Industrie et dans l'Agriculture (F.R.I.A.)
- Fonds National de la Recherche Scientifique (F.N.R.S.)
- Communaute francaise de Belgique-Actions de Recherche Concertees
- DIANE
- Deutsche Forschungsgemeinschaft
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Mitochondria are metabolically highly active cell organelles that are also implicated in reactive oxygen species production and in cell death regulation. Cyclophilin D, the only human mitochondrial isoform of cyclophilins, plays an essential role in the formation of the mitochondrial permeability transition pore leading to cell necrosis. Recently, it has been shown that redox environment modifies structural and functional properties of some plant cyclophilins. Here, it is shown that oxidation of human cyclophilin D influences the conformation of the enzyme but also its activity. Site-directed mutagenized variants of cyclophilin D allowed the identification of cysteine 203 as an important redox-sensitive residue. Moreover, the redox modulation of cyclophilin D was confirmed in human neuroblastoma SH-SY5Y cells exposed to oxidative stress. Altogether, our results suggest that cyclophilin D may play a role as a redox sensor in mitochondria of mammalian cells transmitting information on the redox environment to target proteins. (C) 2009 Elsevier Inc. All rights reserved.
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