Dysfunctional Mitochondria Modulate cAMP-PKA Signaling and Filamentous and Invasive Growth of Saccharomyces cerevisiae
Dysfunctional Mitochondria Modulate cAMP-PKA Signaling and Filamentous and Invasive Growth of Saccharomyces cerevisiae
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DOI：
10.1534/genetics.112.147389
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发表时间：
2013-02-01
期刊：
影响因子：
3.3
通讯作者：
Sedman, Juhan
中科院分区：
文献类型：
--
作者：
Aun, Anu;Tamm, Tiina;Sedman, Juhan
线粒体代谢是介导细胞外部信息的保守信号通路的靶向。然而，很少有人知道线粒体功能障碍是否会干扰信号传导，从而调节细胞对环境变化的反应。在这项研究中，我们分析了有缺陷的丝状和侵入性生长的酵母酿酒酵母菌株，有功能障碍的线粒体基因组（rho突变体）。我们发现rho突变体的形态发生缺陷是由侵袭性和丝状生长所必需的粘附素FLO 11的特异性下调引起的，而不是由细胞器间逆行信号传导引起的一般代谢变化引起的。已知FLO 11的转录受几种信号通路调节，包括促生长特异性MAPK和cAMP活化蛋白激酶A（cAMP-PKA）通路。我们的分析表明，在酵母缺陷的酵母细胞中，生长特异性MAPK通路保留了功能。相反，cAMP-PKA途径下调，也解释了在rho突变体中观察到的各种表型性状。因此，我们的研究结果表明，功能障碍的线粒体调节保守的cAMP-PKA信号通路的输出。
Mitochondrial metabolism is targeted by conserved signaling pathways that mediate external information to the cell. However, less is known about whether mitochondrial dysfunction interferes with signaling and thereby modulates the cellular response to environmental changes. In this study, we analyzed defective filamentous and invasive growth of the yeast Saccharomyces cerevisiae strains that have a dysfunctional mitochondrial genome (rho mutants). We found that the morphogenetic defect of rho mutants was caused by specific downregulation of FLO11, the adhesin essential for invasive and filamentous growth, and did not result from general metabolic changes brought about by interorganellar retrograde signaling. Transcription of FLO11 is known to be regulated by several signaling pathways, including the filamentous-growth-specific MAPK and cAMP-activated protein kinase A (cAMP-PKA) pathways. Our analysis showed that the filamentous-growth-specific MAPK pathway retained functionality in respiratory-deficient yeast cells. In contrast, the cAMP-PKA pathway was downregulated, explaining also various phenotypic traits observed in rho mutants. Thus, our results indicate that dysfunctional mitochondria modulate the output of the conserved cAMP-PKA signaling pathway.