cAMP/PKA signaling balances respiratory activity with mitochondria dependent apoptosis via transcriptional regulation.
cAMP/PKA signaling balances respiratory activity with mitochondria dependent apoptosis via transcriptional regulation.
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DOI：
10.1186/1471-2121-11-92
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发表时间：
2010-11-25
期刊：
影响因子：
--
通讯作者：
Gourlay CW
中科院分区：
文献类型：
--
作者：
Leadsham JE;Gourlay CW
线粒体功能、形态和生物发生的适当控制是真核细胞总体健康的关键决定因素。因此，我们必须了解协调线粒体功能与环境信号系统的机制。PKA活性可以调节酵母线粒体功能对营养变化的响应。不受调节的PKA活性可导致易于产生ROS的线粒体的产生，以及细胞死亡的凋亡形式。我们提出的证据表明，线粒体是敏感的cAMP/PKA信号的水平，可以通过调节呼吸活动的水平或承诺自我执行。酵母PKA催化亚基之一Tpk 3 p的不适当活化足以通过促进功能失调的ROS产生线粒体的产生的转录变化使细胞凋亡死亡。我们的数据表明，cAMP/PKA调节线粒体功能，促进细胞凋亡参与多种转录因子的功能，包括HAP 4，SOK 2和SCO 1。我们提出，在酵母中，是在哺乳动物细胞的情况下，线粒体功能和生物合成控制响应环境变化的协调调节多个转录因子。酵母菌落内cAMP/TPK 3诱导的细胞死亡的可视化支持PKA调节在芽殖酵母中协调呼吸功能和细胞死亡与营养状态中起生理作用的模型。
Appropriate 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. We 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. We 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.
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影响因子：
4
作者：
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