Department of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USA.
Free Radic Biol Med. 2010 Dec 15;49(12):1892-902. doi: 10.1016/j.freeradbiomed.2010.09.014. Epub 2010 Oct 19.
Drosophila mitochondria contain two peroxidases, peroxiredoxin 3 (dPrx3) and peroxiredoxin 5 (dPrx5), which together constitute the sole known intramitochondrial mechanism for the catalytic removal of hydrogen and organic peroxides. dPrx3 exists exclusively within mitochondria, whereas dPrx5 is also present in some other intracellular compartments. Levels of these two peroxiredoxins were genetically manipulated, singly and together, in D. melanogaster, for the purpose of understanding their respective functions. Underexpression of dPrx3 by 90-95% had no discernable effect on life span under normal or oxidative stress conditions; the dPrx5 null flies were previously reported to exhibit a 10% shortening of mean life span and an increase in sensitivity to oxidative stress. Flies underexpressing both dPrx3 and dPrx5 showed an 80% decrease in life span, a severe disruption in thiol homeostasis, and a massive induction of apoptosis in the muscle and digestive system tissues. The early mortality in flies underexpressing both peroxiredoxins was partially offset by overexpression of thioredoxin reductase but not mitochondrion-targeted catalase. These results suggest that mitochondrial peroxiredoxins confer specific protection for thioredoxin/glutathione systems, play a critical role in the maintenance of global thiol homeostasis, and prevent the age-associated apoptosis and premature death.
果蝇的线粒体中含有两种过氧化物酶，过氧化物酶 3（dPrx3）和过氧化物酶 5（dPrx5），它们共同构成了已知的唯一的催化去除氢和有机过氧化物的线粒体内部机制。dPrx3 仅存在于线粒体中，而 dPrx5 也存在于其他一些细胞内隔室中。为了了解它们各自的功能，我们对果蝇中的这两种过氧化物酶进行了基因操作，单独或一起操纵它们的水平。dPrx3 的表达水平降低 90-95%，在正常或氧化应激条件下对寿命没有明显影响；之前报道过 dPrx5 缺失的果蝇平均寿命缩短 10%，对氧化应激的敏感性增加。同时表达水平降低的 dPrx3 和 dPrx5 的果蝇寿命降低了 80%，硫醇稳态严重失调，肌肉和消化系统组织中大量诱导细胞凋亡。过氧化物酶表达水平降低的果蝇的早期死亡率部分被硫氧还蛋白还原酶的过表达所抵消，但线粒体靶向的过氧化氢酶则没有。这些结果表明，线粒体过氧化物酶为硫氧还蛋白/谷胱甘肽系统提供了特定的保护，在维持全局硫醇稳态方面起着关键作用，并防止与年龄相关的凋亡和过早死亡。
