Mitochondrial Thioredoxin System as a Modulator of Cyclophilin D Redox State

被引:47
作者
Folda, Alessandra [1 ]
Citta, Anna [1 ]
Scalcon, Valeria [1 ]
Cali, Tito [1 ]
Zonta, Francesco [3 ]
Scutari, Guido [1 ]
Bindoli, Alberto [2 ]
Rigobello, Maria Pia [1 ]
机构
[1] Univ Padua, Dept Biomed Sci, Via Ugo Bassi 58-B, I-35131 Padua, Italy
[2] CNR, Inst Neurosci, Viale G Colombo 3, I-35131 Padua, Italy
[3] ShanghaiTech Univ, SIAIS, 99 Haike Rd, Shanghai 201210, Peoples R China
来源
SCIENTIFIC REPORTS | 2016年 / 6卷
关键词
PERMEABILITY TRANSITION PORE; OXIDATIVE STRESS; REDUCTASE INHIBITORS; CARBENE COMPLEXES; PHOSPHATE CARRIER; PROTECTS CELLS; ISOMERASE; BINDS; PEROXIREDOXIN; CYCLOSPORINE;
D O I
10.1038/srep23071
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mitochondrial thioredoxin system (NADPH, thioredoxin reductase, thioredoxin) is a major redox regulator. Here we have investigated the redox correlation between this system and the mitochondrial enzyme cyclophilin D. The peptidyl prolyl cis-trans isomerase activity of cyclophilin D was stimulated by the thioredoxin system, while it was decreased by cyclosporin A and the thioredoxin reductase inhibitor auranofin. The redox state of cyclophilin D, thioredoxin 1 and 2 and peroxiredoxin 3 was measured in isolated rat heart mitochondria and in tumor cell lines (CEM-R and HeLa) by redox Western blot analysis upon inhibition of thioredoxin reductase with auranofin, arsenic trioxide, 1-chloro-2,4-dinitrobenzene or after treatment with hydrogen peroxide. A concomitant oxidation of thioredoxin, peroxiredoxin and cyclophilin D was observed, suggesting a redox communication between the thioredoxin system and cyclophilin. This correlation was further confirmed by i) co-immunoprecipitation assay of cyclophilin D with thioredoxin 2 and peroxiredoxin 3, ii) molecular modeling and iii) depleting thioredoxin reductase by siRNA. We conclude that the mitochondrial thioredoxin system controls the redox state of cyclophilin D which, in turn, may act as a regulator of several processes including ROS production and pro-apoptotic factors release.
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页数:11
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