Department of Biochemistry, National University of Singapore, Singapore 117597, Singapore.
Free Radic Biol Med. 2013 Oct;63:381-9. doi: 10.1016/j.freeradbiomed.2013.05.025. Epub 2013 May 28.
The mitochondrial free radical theory of aging proposes that aging is a consequence of progressive mitochondrial dysfunction caused by lifelong accumulation of oxidative damage. Aging is therefore expected to accelerate if the rate of this oxidative damage accumulation increases. Studies attempting to test this prediction through modulation of oxidative damage by altering antioxidant defenses have reported conflicting results. Here we investigated the effects of repressing prdx-3, responsible for the detoxification of mitochondrial hydrogen peroxide, in developmentally normal wild-type Caenorhabditis elegans. We report that life span and levels of oxidative protein damage were not altered when prdx-3 was repressed in adult nematodes. We further found evidence that mitochondrial uncoupling increased in response to repression of prdx-3. Nevertheless repression of prdx-3 led to reductions in steady-state levels of ATP, motility, and brood size, indicating the importance of this enzyme to normal life in C. elegans.
衰老的线粒体自由基理论提出，衰老是由于一生中氧化损伤的积累导致线粒体功能逐渐丧失的结果。因此，如果这种氧化损伤积累的速度加快，衰老预计会加速。通过改变抗氧化防御来改变氧化损伤来测试这一预测的研究报告结果相互矛盾。在这里，我们通过抑制参与清除线粒体过氧化氢的 prdx-3 来研究其在发育正常的野生型秀丽隐杆线虫中的作用。我们报告说，当 prdx-3 在成年线虫中被抑制时，寿命和氧化蛋白损伤水平没有改变。我们进一步发现，抑制 prdx-3 会导致线粒体解偶联增加。然而，prdx-3 的抑制导致 ATP 水平、运动能力和产卵量的稳定降低，这表明该酶对秀丽隐杆线虫的正常生命至关重要。
