Linard Dominique, Kandlbinder Andrea, Degand Hervé, Morsomme Pierre, Dietz Karl-Josef, Knoops Bernard
Laboratory of Cell Biology, Institut des Sciences de la Vie, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
Arch Biochem Biophys. 2009 Nov;491(1-2):39-45. doi: 10.1016/j.abb.2009.09.002. Epub 2009 Sep 6.
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.
线粒体是代谢高度活跃的细胞器，也与活性氧的产生和细胞死亡调控有关。亲环蛋白D是亲环蛋白唯一的人类线粒体同种型，在导致细胞坏死的线粒体通透性转换孔的形成中起重要作用。最近，有研究表明氧化还原环境会改变一些植物亲环蛋白的结构和功能特性。在此研究中发现，人类亲环蛋白D的氧化不仅会影响该酶的构象，还会影响其活性。亲环蛋白D的定点诱变变体确定了半胱氨酸203是一个重要的氧化还原敏感残基。此外，在暴露于氧化应激的人类神经母细胞瘤SH-SY5Y细胞中证实了亲环蛋白D的氧化还原调节作用。总之，我们的结果表明，亲环蛋白D可能在哺乳动物细胞的线粒体中作为氧化还原传感器发挥作用，将氧化还原环境的信息传递给靶蛋白。
