Ubiquitin-Conjugating Enzymes Ubc1 and Ubc4 Mediate the Turnover of Hap4, a Master Regulator of Mitochondrial Biogenesis in Saccharomyces cerevisiae.
Ubiquitin-Conjugating Enzymes Ubc1 and Ubc4 Mediate the Turnover of Hap4, a Master Regulator of Mitochondrial Biogenesis in Saccharomyces cerevisiae.
复制标题
DOI：
10.3390/microorganisms10122370
复制
发表时间：
2022-11-30
期刊：
影响因子：
4.5
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Capps D;Hunter A;Chiang M;Pracheil T;Liu Z
线粒体的生物发生受到严格的调控，以响应细胞外和细胞内的信号，从而使酵母细胞适应环境的变化。Hap2/3/4/5复合体是酵母线粒体生物发生的主要转录调控因子。HAP4是该复合体的调节亚单位，当Hap2/3/4/5复合体被激活时，HAP4的表达增加。在葡萄糖去抑制条件下生长的细胞中，HAP4转录水平和HAP4蛋白水平都增加。作为协调线粒体和核基因组之间基因表达的细胞器间信号机制的一部分，在呼吸缺陷细胞中，如缺乏线粒体DNA的ρ0细胞，由于HAP4蛋白水平的降低，HAP2/3/4/5复合体的活性降低。然而，潜在的机制尚不清楚。在这里，我们证明了HAP4在ρ0细胞中的表达减少是通过转录和转录后机制来调节的。我们发现线粒体DNA的丢失增加了Hap4的周转，这需要26S蛋白酶体和泛素结合酶Ubc1和Ubc4。Hap4在ubc1/ubc4双突变体中的稳定导致Hap2/3/4/5靶基因表达增加。我们的结果表明，酵母中线粒体的生物发生部分是由线粒体的功能状态调节的，部分是通过依赖泛素/蛋白酶体的Hap4的周转来实现的。
Mitochondrial biogenesis is tightly regulated in response to extracellular and intracellular signals, thereby adapting yeast cells to changes in their environment. The Hap2/3/4/5 complex is a master transcriptional regulator of mitochondrial biogenesis in yeast. Hap4 is the regulatory subunit of the complex and exhibits increased expression when the Hap2/3/4/5 complex is activated. In cells grown under glucose derepression conditions, both the HAP4 transcript level and Hap4 protein level are increased. As part of an inter-organellar signaling mechanism coordinating gene expression between the mitochondrial and nuclear genomes, the activity of the Hap2/3/4/5 complex is reduced in respiratory-deficient cells, such as ρ0 cells lacking mitochondrial DNA, as a result of reduced Hap4 protein levels. However, the underlying mechanism is unclear. Here, we show that reduced HAP4 expression in ρ0 cells is mediated through both transcriptional and post-transcriptional mechanisms. We show that loss of mitochondrial DNA increases the turnover of Hap4, which requires the 26S proteasome and ubiquitin-conjugating enzymes Ubc1 and Ubc4. Stabilization of Hap4 in the ubc1 ubc4 double mutant leads to increased expression of Hap2/3/4/5-target genes. Our results indicate that mitochondrial biogenesis in yeast is regulated by the functional state of mitochondria partly through ubiquitin/proteasome-dependent turnover of Hap4.
登录
查看更多内容
影响因子：
4.8
作者：
Bouchez, Cyrielle L.;Yoboue, Edgar D.;Devin, Anne
通讯作者：
Devin, Anne
影响因子：
--
作者：
Buschlen, S;Amillet, JM;Bolotin-Fukuhara, M
通讯作者：
Bolotin-Fukuhara, M
影响因子：
10.5
作者：
FORSBURG, SL;GUARENTE, L
通讯作者：
GUARENTE, L
DOI：
10.1073/pnas.032516399
发表时间：
2002-02-05
影响因子：
11.1
作者：
Fleming, JA;Lightcap, ES;Blackman, RK
通讯作者：
Blackman, RK
影响因子：
3.5
作者：
Devaux, F;Carvajal, E;Jacq, C
通讯作者：
Jacq, C