Mitochondria-to-nuclear signaling is regulated by the subcellular localization of the transcription factors Rtg1p and Rtg3p.
Mitochondria-to-nuclear signaling is regulated by the subcellular localization of the transcription factors Rtg1p and Rtg3p.
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DOI：
10.1091/mbc.11.6.2103
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发表时间：
2000-06
影响因子：
3.3
通讯作者：
Takayuki Sekito;Janet M. Thornton;R. A. Butow
中科院分区：
文献类型：
--
作者：
Takayuki Sekito;Janet M. Thornton;R. A. Butow
细胞调节核基因的表达，以响应线粒体功能状态的变化，这是一种称为逆行调节的细胞器间通讯途径。在酵母中，CIT 2基因的表达显示出典型的逆行反应，因为其表达在具有功能障碍的线粒体的细胞中显著增加，例如在rho（o）petites中。三个基因控制该信号通路：RTG 1和RTG 3，其编码碱性螺旋-环-螺旋亮氨酸拉链转录因子，其作为异二聚体结合到CIT 2上游激活位点，以及RTG 2，其编码未知功能的蛋白质。我们发现，在CIT 2表达低的表达能力（rho（+））细胞中，Rtg 1 p和Rtg 3 p主要在细胞质中作为复合物存在，而在CIT 2表达高的rho（o）petites中，它们作为复合物主要存在于细胞核中。细胞质Rtg 3 p是多重磷酸化的，当定位在细胞核中时，变得部分去磷酸化。Rtg 2 p在rho（+）和rho（o）细胞中均位于胞质内，是Rtg 3 p去磷酸化和核定位所必需的。Rtg 3 p与Rtg 1 p的相互作用是将Rtg 3 p保留在rho（+）细胞的细胞质中所必需的;在没有这种相互作用的情况下，Rtg 3 p的核定位和去磷酸化独立于Rtg 2 p。我们的数据表明，Rtg 1 p作为一个积极的和消极的调节器的逆行反应和Rtg 2 p的行为，以抑制线粒体信号影响磷酸化状态和亚细胞定位的Rtg 3 p。
Cells modulate the expression of nuclear genes in response to changes in the functional state of mitochondria, an interorganelle communication pathway called retrograde regulation. In yeast, expression of the CIT2 gene shows a typical retrograde response in that its expression is dramatically increased in cells with dysfunctional mitochondria, such as in rho(o) petites. Three genes control this signaling pathway: RTG1 and RTG3, which encode basic helix-loop-helix leucine zipper transcription factors that bind as heterodimer to the CIT2 upstream activation site, and RTG2, which encodes a protein of unknown function. We show that in respiratory-competent (rho(+)) cells in which CIT2 expression is low, Rtg1p and Rtg3p exist as a complex largely in the cytoplasm, and in rho(o) petites in which CIT2 expression is high, they exist as a complex predominantly localized in the nucleus. Cytoplasmic Rtg3p is multiply phosphorylated and becomes partially dephosphorylated when localized in the nucleus. Rtg2p, which is cytoplasmic in both rho(+) and rho(o) cells, is required for the dephosphorylation and nuclear localization of Rtg3p. Interaction of Rtg3p with Rtg1p is required to retain Rtg3p in the cytoplasm of rho(+) cells; in the absence of such interaction, nuclear localization and dephosphorylation of Rtg3p is independent of Rtg2p. Our data show that Rtg1p acts as both a positive and negative regulator of the retrograde response and that Rtg2p acts to transduce mitochondrial signals affecting the phosphorylation state and subcellular localization of Rtg3p.