线粒体功能的改变与多种细胞和生物体应激反应有关,包括细胞凋亡。老化,神经变性和肿瘤发生。然而,对线粒体功能障碍的适应可以通过激活存活途径发生,其机制仍然知之甚少。酿酒酵母是研究线粒体功能障碍如何影响应激反应和适应过程的宝贵模型生物。在这项研究中,我们分析并比较了在不存在和存在渗透应激野生型细胞的情况下,缺乏线粒体DNA的两种细胞模型:溴化乙锭处理的细胞(ρ0)和缺乏线粒体嘧啶核苷酸转运蛋白RIM2(ΔRIM2)的细胞。我们的结果表明,线粒体DNA的缺乏在应激反应的动力学方面具有优势。此外,在存在呼吸代谢的情况下,野生型细胞表现出更高的渗透敏感性。线粒体突变体显示甘油水平升高,在酵母渗透适应的短期反应中需要,和长期的氧化应激。先前已经证明了线粒体逆行信号传导参与渗透适应。CIT2的表达,编码柠檬酸合酶的过氧化物酶体同工型,其上调是RTG途径激活的原型,在突变体中似乎增加了。有趣的是,选择的TCA周期基因,CIT1和ACO1,其表达取决于应激时的RTG信号传导,在ρ0和ΔRIM2细胞中显示出不同的调节。这些数据表明,在存在线粒体缺陷的情况下,渗透适应可以通过不同的机制发生,并将使我们能够深入了解代谢之间的关系。线粒体介导的应激反应,细胞适应。
Alterations in mitochondrial function have been linked to a variety of cellular and organismal stress responses including apoptosis, aging, neurodegeneration and tumorigenesis. However, adaptation to mitochondrial dysfunction can occur through the activation of survival pathways, whose mechanisms are still poorly understood. The yeast Saccharomyces cerevisiae is an invaluable model organism for studying how mitochondrial dysfunction can affect stress response and adaptation processes. In this study, we analyzed and compared in the absence and in the presence of osmostress wild-type cells with two models of cells lacking mitochondrial DNA: ethidium bromide-treated cells (ρ0) and cells lacking the mitochondrial pyrimidine nucleotide transporter RIM2 (ΔRIM2). Our results revealed that the lack of mitochondrial DNA provides an advantage in the kinetics of stress response. Additionally, wild-type cells exhibited higher osmosensitivity in the presence of respiratory metabolism. Mitochondrial mutants showed increased glycerol levels, required in the short-term response of yeast osmoadaptation, and prolonged oxidative stress. The involvement of the mitochondrial retrograde signaling in osmoadaptation has been previously demonstrated. The expression of CIT2, encoding the peroxisomal isoform of citrate synthase and whose up-regulation is prototypical of RTG pathway activation, appeared to be increased in the mutants. Interestingly, selected TCA cycle genes, CIT1 and ACO1, whose expression depends on RTG signaling upon stress, showed a different regulation in ρ0 and ΔRIM2 cells. These data suggest that osmoadaptation can occur through different mechanisms in the presence of mitochondrial defects and will allow us to gain insight into the relationships among metabolism, mitochondria-mediated stress response, and cell adaptation.