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Subcell Biochem. 2012;57:79-100. doi: 10.1007/978-94-007-2561-4_4.

The Retrograde ResponseRetrograde Response and Other Pathways of Interorganelle CommunicationInterorganelle Communication in Yeast Replicative Aging.

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  • 1Department of Medicine, Tulane University Health Sciences Center, Tulane Center for Aging, Tulane University, New Orleans, LA, 70112, USA, sjazwins@tulane.edu.


A form of mitochondria-to-nucleus signalingmitochondria-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 dysfunctionmitochondrial 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 mitophagymitophagy , which appear to be involved in mitochondrial quality controlmitochondrial quality control . This plethora of mitochondrial surveillancemitochondrial surveillance mechanisms points to the central importance of this organelleorganelle in yeast replicative aging. Additional pathwayspathways that monitor mitochondrial statusmitochondrial status that do not apparently involve the retrograde response machinery also play a role. A unifying theme is the involvement of the target of rapamycintarget of rapamycin (TORTOR ) in both these additional pathways and in the retrograde response. The involvement of TOR brings another large family of signaling events into juxtaposition. CeramideCeramide 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 regulationmetabolic regulation , stress resistancestress resistance , chromatin-dependent gene regulationchromatin-dependent gene regulation , and genome stabilitygenome 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 cellsmammalian cells . The retrograde response is a prototypical pathway of interorganelle communication. Other such phenomena are emerging, such as the cross-talkcross-talk between mitochondriamitochondria and the vacuolevacuole , which involves components of the retrograde signaling pathway. The impact of these varied physiological responses on yeast replicative aging remains to be assessed.

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