Centre National de la Recherche Scientifique, Centre de Génétique Moléculaire, Gif-sur-Yvette, France.
Exp Gerontol. 2010 Aug;45(7-8):543-9. doi: 10.1016/j.exger.2010.01.012. Epub 2010 Jan 22.
In the filamentous fungus Podospora anserina, aging is systematically associated with mitochondrial DNA (mtDNA) instability. A causal link between deficiency of the cytochrome respiratory pathway and lifespan extension has been demonstrated. Knock out of the cytochrome respiratory pathway induces the expression of an alternative oxidase and is associated with a reduction in free radical production. The question of the links between mtDNA stability, ROS generation and lifespan is therefore clearly raised in this organism. NADPH lies at the heart of many anti-oxidant defenses of the cell. In Saccharomyces cerevisiae, the mitochondrial NADPH is largely provided by the Pos5 NADH kinase. We show here that disruption of PaNdk1 encoding the potential mitochondrial NADH kinase of P. anserina leads to severe somatic and sexual defects and to hypersensitivity to hydrogen peroxide and paraquat. Surprisingly, it also leads to a spectacular increase of mtDNA stability and lifespan. We propose that an adaptative metabolic change including the induction of the alternative oxidase can account for these results.
在丝状真菌伞滑锈伞（Podospora anserina）中，衰老与线粒体 DNA（mtDNA）不稳定性系统相关。已经证明细胞色素呼吸途径的缺陷与寿命延长之间存在因果关系。细胞色素呼吸途径的敲除会诱导替代氧化酶的表达，并与自由基产生的减少相关。因此，在这种生物体中，mtDNA 稳定性、ROS 生成和寿命之间的联系问题被明确提出。NADPH 位于细胞许多抗氧化防御的核心。在酿酒酵母（Saccharomyces cerevisiae）中，线粒体 NADPH 主要由 Pos5 NADH 激酶提供。我们在这里表明，破坏编码伞滑锈伞潜在线粒体 NADH 激酶的 PaNdk1 会导致严重的体细胞和有性缺陷，并对过氧化氢和百草枯敏感。令人惊讶的是，它还导致 mtDNA 稳定性和寿命的显著增加。我们提出，包括诱导替代氧化酶在内的适应性代谢变化可以解释这些结果。
