cAMP/PKA signaling balances respiratory activity with mitochondria dependent apoptosis via transcriptional regulation

BMC Cell Biology

Research Article

Jane E Leadsham¹  Campbell W Gourlay¹ 

[1] Department of Biosciences, University of Kent, Canterbury Kent, CT2 7NJ, England, UK;

关键词: Reactive Oxygen Species Production;    Mitochondrial Biogenesis;    Electron Transport System;    Diauxic Shift;    cAMP Elevation;   

DOI  :  10.1186/1471-2121-11-92

 received in 2010-09-01, accepted in 2010-11-25,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundAppropriate control of mitochondrial function, morphology and biogenesis are crucial determinants of the general health of eukaryotic cells. It is therefore imperative that we understand the mechanisms that co-ordinate mitochondrial function with environmental signaling systems. The regulation of yeast mitochondrial function in response to nutritional change can be modulated by PKA activity. Unregulated PKA activity can lead to the production of mitochondria that are prone to the production of ROS, and an apoptotic form of cell death.ResultsWe present evidence that mitochondria are sensitive to the level of cAMP/PKA signaling and can respond by modulating levels of respiratory activity or committing to self execution. The inappropriate activation of one of the yeast PKA catalytic subunits, Tpk3p, is sufficient to commit cells to an apoptotic death through transcriptional changes that promote the production of dysfunctional, ROS producing mitochondria. Our data implies that cAMP/PKA regulation of mitochondrial function that promotes apoptosis engages the function of multiple transcription factors, including HAP4, SOK2 and SCO1.ConclusionsWe propose that in yeast, as is the case in mammalian cells, mitochondrial function and biogenesis are controlled in response to environmental change by the concerted regulation of multiple transcription factors. The visualization of cAMP/TPK3 induced cell death within yeast colonies supports a model that PKA regulation plays a physiological role in coordinating respiratory function and cell death with nutritional status in budding yeast.

【 授权许可】

CC BY   
© Leadsham and Gourlay; licensee BioMed Central Ltd. 2010