Impact of ROS signalling and ROS scavenging on aging and development of the ascomycete Podospora anserina

在任何生物体的生命周期中形成的活性氧（ROS）在细胞信号传导中是活跃的，但也引起分子损伤。虽然已知第一个过程与发育相关，但ROS诱导的损伤的时间依赖性累积被认为是理解衰老的关键。最近，当研究真菌衰老模型Podospora anserina中的超氧化物歧化酶（SOD）时，我们获得了意想不到的结果，这一观点受到质疑：（i）发现三个SOD基因的缺失菌株是可行的，（ii）编码线粒体SOD的基因（PaSOD 3）的过表达是有害的。PaSOD 3过表达的初步表征揭示了PaSOD 3水平增加对分子监测系统不同组分的影响。现在，我们的目标是解决潜在的机制，以阐明ROS信号与ROS损伤对衰老和发育的影响。首先，现有的菌株与改变SOD水平的研究方面的ROS水平和生产，ROS诱导的损伤和细胞监视途径的选定组件的表达和丰度的影响。其次，分析在标准条件下生长或受到氧化应激攻击的不同年龄的野生型菌株，以鉴定菌株寿命期间的系统变化。从这些研究中，我们期望确定控制衰老和发育的新分子途径，以及它们的组分之间的相互作用，这大大超出了关于ROS在这些基本过程中的作用的最新知识。

Reactive oxygen species (ROS) formed during the lifespan of any organism are active in cellular signaling but also cause molecular damage. While the first process is known to be relevant for development, the time-dependent accumulation of ROS-induced damage is considered to be a key for understanding aging. Recently, when studying superoxide dismutases (SODs) in the fungal aging model Podospora anserina, we obtained unexpected results which question this view: (i) deletion strains of the three SOD genes were found to be viable, and (ii) over-expression of the gene coding for the mitochondrial SOD (PaSOD3) was detrimental. The initial characterization of PaSod3 overexpressors revealed an impact of increased PaSOD3 levels on different components of the molecular surveillance system. Now we aim to address the underlying mechanisms to elucidate the impact of ROS signaling vs. ROS damaging on aging and development. First, existing strains with altered SOD level are studied with respect to ROS levels and production, ROS-induced damage and the impact on the expression and abundance of selected components of cellular surveillance pathways. Second, wild-type strains of different age grown under standard conditions or challenged by oxidative stress are analyzed to identify systematic changes during the lifetime of strains. From these investigations we expect to identify new molecular pathways controlling aging and development and interactions between components of them going considerably beyond the state-of-the-art of knowledge about the role of ROS in these fundamental processes.