Autophagy and amino acid homeostasis are required for chronological longevity in Saccharomyces cerevisiae.
Autophagy and amino acid homeostasis are required for chronological longevity in Saccharomyces cerevisiae.
复制标题
DOI：
10.1111/j.1474-9726.2009.00469.x
复制
发表时间：
2009-08
期刊：
影响因子：
7.8
通讯作者：
Aris JP
中科院分区：
文献类型：
--
作者：
Alvers AL;Fishwick LK;Wood MS;Hu D;Chung HS;Dunn WA Jr;Aris JP
停止生长后，酵母细胞在非分裂状态下保持活力，持续一段时间，称为时序寿命（CLS）。自噬是一种降解过程，负责响应氮饥饿和氨基酸限制的氨基酸再循环。我们研究了在含有不同补充必需和非必需氨基酸的葡萄糖基本培养基中生长的酵母在时间老化过程中自噬的作用。自噬所需的ATG1或ATG7的缺失会降低CLS，而细胞组分选择性靶向液泡降解所需的ATG11的缺失不会降低CLS。非必需氨基酸异亮氨酸和缬氨酸以及必需氨基酸亮氨酸在自噬缺陷以及自噬感受态酵母中延长CLS。这种延伸受到GCN 4的组成型表达的抑制，GCN 4编码一般氨基酸控制（GAAC）的转录调节因子。与此一致，GCN 4表达被异亮氨酸和缬氨酸降低。此外，亮氨酸需求的消除延长了CLS并防止了GCN 4组成型表达的影响。有趣的是，缺失LEU3（编码支链侧链氨基酸合成的转录调节因子的GAAC靶基因）在不存在氨基酸补充物的情况下显著增加CLS。一般而言，这表明GAAC的活化降低CLS，而GAAC的抑制延长基本培养基中的CLS。这些发现表明自噬和氨基酸稳态在决定酵母CLS中的重要作用。
Following cessation of growth, yeast cells remain viable in a non-dividing state for a period of time known as the chronological life span (CLS). Autophagy is a degradative process responsible for amino acid recycling in response to nitrogen starvation and amino acid limitation. We have investigated the role of autophagy during chronological aging of yeast grown in glucose minimal media containing different supplemental essential and non-essential amino acids. Deletion of ATG1 or ATG7, both of which are required for autophagy, reduces CLS, whereas deletion of ATG11, which is required for selective targeting of cellular components to the vacuole for degradation, does not reduce CLS. The non-essential amino acids isoleucine and valine, and the essential amino acid leucine, extend CLS in autophagy-deficient as well as autophagy-competent yeast. This extension is suppressed by constitutive expression of GCN4, which encodes a transcriptional regulator of general amino acid control (GAAC). Consistent with this, GCN4 expression is reduced by isoleucine and valine. Furthermore, elimination of the leucine requirement extends CLS and prevents the effects of constitutive expression of GCN4. Interestingly, deletion of LEU3, a GAAC target gene encoding a transcriptional regulator of branched side chain amino acid synthesis, dramatically increases CLS in the absence of amino acid supplements. In general, this indicates that activation of GAAC reduces CLS whereas suppression of GAAC extends CLS in minimal medium. These findings demonstrate important roles for autophagy and amino acid homeostasis in determining CLS in yeast.
登录
查看更多内容
影响因子：
7.4
作者：
Chen, QH;Thorpe, J;Keller, JN
通讯作者：
Keller, JN
影响因子：
13.3
作者：
Juhasz, Gabor;Neufeld, Thomas P.
通讯作者：
Neufeld, Thomas P.
影响因子：
2.1
作者：
Cohen, Ruth;Engelberg, David
通讯作者：
Engelberg, David
DOI：
10.1083/jcb.200604072
发表时间：
2006-07-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Allen C;Büttner S;Aragon AD;Thomas JA;Meirelles O;Jaetao JE;Benn D;Ruby SW;Veenhuis M;Madeo F;Werner-Washburne M
通讯作者：
Werner-Washburne M
ATG11将ATG9募集到脑吞噬体结构中对于萌芽酵母的选择性自噬至关重要。
影响因子：
7.8
作者：
He, Congcong;Song, Hui;Yorimitsu, Tomohiro;Monastyrska, Iryna;Yen, Wei-Lien;Legakis, Julie E;Klionsky, Daniel J
通讯作者：
Klionsky, Daniel J