Jazwinski S Michal
Department of Medicine, Tulane University Health Sciences Center, Tulane Center for Aging, Tulane University, New Orleans, LA, 70112, USA,
Subcell Biochem. 2012;57:79-100. doi: 10.1007/978-94-007-2561-4_4.
A form of mitochondria-to-nucleus signaling mitochondria-to-nucleus signaling is known to play a role in determining replicative life span in yeast. This retrograde response is triggered by experimentally-induced mitochondrial dysfunction mitochondrial dysfunction, but it also is activated during the course of normal replicative aging, allowing yeast to have as long a replicative life span as they do. The components of the retrograde signaling pathway participate in diverse cellular processes such as mitophagy, which appear to be involved in mitochondrial quality control mitochondrial quality control. This plethora of mitochondrial surveillance mitochondrial surveillance mechanisms points to the central importance of this organelle organelle in yeast replicative aging. Additional pathways pathways that monitor mitochondrial status mitochondrial status that do not apparently involve the retrograde response machinery also play a role. A unifying theme is the involvement of the target of rapamycin target of rapamycin (TOR) in both these additional pathways and in the retrograde response. The involvement of TOR brings another large family of signaling events into juxtaposition. Ceramide synthesis is regulated by TOR opening up the potential for coordination of mitochondrial status with a wide array of additional cellular processes. The retrograde response lies at the nexus of metabolic regulation metabolic regulation, stress resistance stress resistance, chromatin-dependent gene regulation chromatin-dependent gene regulation, and genome stability genome stability. In its metabolic outputs, it is related to calorie restriction,calorie restriction, which may be the result of the involvement of TOR. Retrograde response-like processes have been identified in systems other than yeast, including mammalian cells mammalian cells. The retrograde response is a prototypical pathway of interorganelle communication. Other such phenomena are emerging, such as the cross-talk cross-talk between mitochondria mitochondria and the vacuole vacuole, which involves components of the retrograde signaling pathway. The impact of these varied physiological responses on yeast replicative aging remains to be assessed.
一种线粒体到细胞核的信号传导形式 已知线粒体到细胞核的信号传导在决定酵母的复制寿命中起作用。这种逆行反应由实验诱导的线粒体功能障碍引发，但在正常复制衰老过程中也会被激活，使酵母具有与实际相同的复制寿命。逆行信号通路的成分参与多种细胞过程，如线粒体自噬，这似乎与线粒体质量控制有关。大量的线粒体监测机制表明该细胞器在酵母复制衰老中至关重要。其他监测线粒体状态的途径显然不涉及逆行反应机制，但也发挥作用。一个统一的主题是雷帕霉素靶蛋白（TOR）在这些额外途径和逆行反应中均有参与。TOR的参与使另一大信号事件家族并列出现。神经酰胺合成受TOR调节，为线粒体状态与大量其他细胞过程的协调创造了可能性。逆行反应处于代谢调节、应激抗性、染色质依赖性基因调节和基因组稳定性的交汇点。在其代谢输出方面，它与热量限制有关，热量限制可能是TOR参与的结果。在酵母以外的系统中也发现了类似逆行反应的过程，包括哺乳动物细胞。逆行反应是细胞器间通讯的典型途径。其他此类现象也在出现，如线粒体与液泡之间的相互作用，这涉及逆行信号通路的成分。这些不同生理反应对酵母复制衰老的影响仍有待评估。
