Sundaram Venkatraghavan, Petkova Mima I, Pujol-Carrion Nuria, Boada Jordi, de la Torre-Ruiz Maria Angeles
Department of Basic Medical Sciences, IRB-Lleida, University of Lleida, Av. Alcalde Rovira Roure n° 80, 25198, Lleida, Spain.
Department of Experimental Medicine, IRB-Lleida, University of Lleida, Av. Alcalde Rovira Roure n° 80, 25198, Lleida, Spain.
Mol Microbiol. 2015 Jul;97(1):93-109. doi: 10.1111/mmi.13013. Epub 2015 May 15.
Here we show that Mtl1, member of the cell wall integrity pathway of Saccharomyces cerevisiae, plays a positive role in chronological life span (CLS). The absence of Mtl1 shortens CLS and causes impairment in the mitochondrial function. This is reflected in a descent in oxygen consumption during the postdiauxic state, an increase in the uncoupled respiration and mitochondrial membrane potential and also a descent in aconitase activity. We demonstrate that all these effects are a consequence of signalling defects suppressed by TOR1 (target of rapamycin) and SCH9 deletion and less efficiently by Protein kinase A (PKA) inactivation. Mtl1 also plays a role in the regulation of both Bcy1 stability and phosphorylation, mainly in response to glucose depletion. In postdiauxic phase and in conditions of glucose depletion, Mtl1 negatively regulates TOR1 function leading to Sch9 inactivation and Bcy1 phosphorylation converging in PKA inhibition. Slt2/Mpk1 kinase partially contributes to Bcy1 phosphorylation, although additional targets are not excluded. Mtl1 links mitochondrial dysfunction with TOR and PKA pathways in quiescence, glucose being the main signalling molecule.
在此我们表明，酿酒酵母细胞壁完整性途径的成员Mtl1在时序寿命（CLS）中发挥积极作用。Mtl1的缺失会缩短CLS并导致线粒体功能受损。这表现为在二次生长后期状态下氧气消耗下降、解偶联呼吸和线粒体膜电位增加，以及乌头酸酶活性下降。我们证明，所有这些效应都是由雷帕霉素靶蛋白（TOR1）和SCH9缺失抑制的信号缺陷导致的，而蛋白激酶A（PKA）失活对其抑制作用较弱。Mtl1在Bcy1稳定性和磷酸化的调节中也发挥作用，主要是对葡萄糖耗竭作出反应。在二次生长后期阶段和葡萄糖耗竭的条件下，Mtl1负向调节TOR1功能，导致Sch9失活和Bcy1磷酸化，最终抑制PKA。Slt2/Mpk1激酶部分促进Bcy1磷酸化，尽管不排除存在其他靶点。在静止状态下，Mtl1将线粒体功能障碍与TOR和PKA途径联系起来，葡萄糖是主要的信号分子。
