Evidence for the bifunctional nature of mitochondrial phosphatidylserine decarboxylase:: Role in Pdr3-dependent retrograde regulation of PDR5 expression
Evidence for the bifunctional nature of mitochondrial phosphatidylserine decarboxylase:: Role in Pdr3-dependent retrograde regulation of PDR5 expression
复制标题
DOI：
10.1128/mcb.00405-08
复制
发表时间：
2008-10-01
影响因子：
5.3
通讯作者：
Moye-Rowley, W. Scott
中科院分区：
文献类型：
--
作者：
Gulshan, Kailash;Schmidt, Jennifer A.;Moye-Rowley, W. Scott
酵母的多药耐药对细胞线粒体基因组状态敏感。失去细胞器基因组的细胞（[rho(0)]细胞）通过增加含有锌簇的转录因子Pdr3的表达，显著诱导多种或多性耐药基因的转录。Pdr3的一个主要靶基因是atp结合盒转运蛋白编码基因PDR5。Pdr5已被证明是一种磷脂酶，可催化磷脂酰乙醇胺（PE）的净向外运动。由于线粒体定位的Psd1酶提供了PE生物合成的主要途径，我们评估了Psd1功能与PDR5调节之间的潜在联系。在野生型（[rho(+)]）细胞中过量产生Psd1可诱导PDR5转录并以pdr3依赖的方式产生耐药性。[rho(0)]细胞中PSD1基因的缺失阻止了PDR5表达的正常激活。令人惊讶的是，Psd1的无催化活性形式的表达仍然支持PDR5的转录激活，这表明PE水平不是触发PDR5诱导的信号。绿色荧光蛋白融合的表达将诱导PDR5表达所需的区域映射到Psd1的非催化氨基末端部分。Psd1是PE生物合成和多药耐药调控所必需的新型双功能蛋白。
Multidrug resistance in the yeast Saccharomyces cerevisiae is sensitive to the mitochondrial genome status of cells. Cells that lose their organellar genome ([rho(0)] cells) dramatically induce transcription of multiple or pleiotropic drug resistance genes via increased expression of a zinc cluster-containing transcription factor designated Pdr3. A major Pdr3 target gene is the ATP-binding cassette transporter-encoding gene PDR5. Pdr5 has been demonstrated to act as a phospholipid floppase catalyzing the net outward movement of phosphatidylethanolamine (PE). Since the mitochondrially localized Psd1 enzyme provides a major route of PE biosynthesis, we evaluated the potential linkage between Psd1 function and PDR5 regulation. Overproduction of Psd1 in wild-type ([rho(+)]) cells was found to induce PDR5 transcription and drug resistance in a Pdr3-dependent manner. Loss of the PSD1 gene from [rho(0)] cells prevented the normal activation of PDR5 expression. Surprisingly, expression of a catalytically inactive form of Psd1 still supported PDR5 transcriptional activation, suggesting that PE levels were not the signal triggering PDR5 induction. Expression of green fluorescent protein fusions mapped the region required to induce PDR5 expression to the noncatalytic amino-terminal portion of Psd1. Psd1 is a novel bifunctional protein required both for PE biosynthesis and regulation of multidrug resistance.