The Perception of Mitochondrial Stress in Receiving Cells

最近发现，神经元细胞中ETC信号的减少足以延长C. 优雅还发现，这种效应取决于细胞的基本组分的活性。 线粒体应激反应或UPRmt。然而，目前还不清楚， 这种寿命延长发生在哪一个或信号如何被发送和感知。此外， 在细胞内稳态和能量生产中，它可能起反应性作用， 能够影响生物体对疾病的易感性的随机内在或外在变量的传感器。 因此，线粒体内的变化也可能是导致这些细胞中显示出的紧急特性的原因。 系统响应随机变化，和/或可能在协调激活 非线粒体应激反应途径。预测基因改造将降低 因为线粒体功能的随机变化最终会对生物体的适应性产生负面影响。 这种假设与最近的证据相一致，这些证据表明有害突变实际上会减少 基因表达对微小环境变化的敏感性（表型丧失） 鲁棒性）。进一步的假设是，它可以预测UPRmt和应激反应之间的协方差 途径，目前认为在不同的调控网络中起作用，并寻求发现潜在的 这种协方差发生的机制。

It was recently discovered that reduced ETC signaling in neuronal cells is sufficient to extend the lifespan of C. elegans. It was also found that this effect is dependent upon the activity of an essential component of the mitochondrial stress response or UPRmt. It is not yet understood, however, the fundamental mechanisms by which this life span extension occurs or how the signal is sent and perceived. Moreover, the essential role that the mitochondrion has in cellular homeostasis and energy production suggests that it may act as a reactive sensor of random intrinsic or extrinsic variables capable of influencing an organism's susceptibility to disease. Changes within the mitochondria thus also might be responsible for the emergent properties displayed in such a system in response to stochastic changes, and/or may play a significant role in coordinating the activation of non-mitochondrial stress response pathways. A prediction that genetic modifications will decrease the capacity for stochastic variation in mitochondrial function will ultimately negatively affect the fitness of the organism. Such a hypothesis is in keeping with recent evidence suggesting that deleterious mutations actually decrease the sensitivity of gene expression in response to small environmental changes (a loss of phenotypic robustness). A further hypothesis is it may predict co-variance between the UPRmt and stress response pathways, currently thought to act in distinct regulatory networks, and seek to discover the potential mechanisms by which this co-variance occurs.