Redox characterization of human cyclophilin D: identification of a new mammalian mitochondrial redox sensor?
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.
Linard
Dominique
D
Laboratory of Cell Biology, Institut des Sciences de la Vie, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
Kandlbinder
Andrea
A
Degand
Hervé
H
Morsomme
Pierre
P
Dietz
Karl-Josef
KJ
Knoops
Bernard
B
D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003545:Cysteine; D015180:Electrophoresis, Gel, Two-Dimensional; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D010084:Oxidation-Reduction; D011487:Protein Conformation; D016415:Sequence Alignment; D013050:Spectrometry, Fluorescence; D014364:Tryptophan
D000081406:Peptidyl-Prolyl Isomerase F; D014364:Tryptophan; D006861:Hydrogen Peroxide; D021983:Cyclophilins; D003545:Cysteine