Centro Andaluz de Biología Molecular y Medicina Regenerativa, Universidad de Sevilla, Avda. Américo Vespucio s/n, 41092 Sevilla, Spain.
Departamento de Genética, Universidad de Sevilla, Avda. Reina Mercedes 6, 41012 Sevilla, Spain.
Int J Mol Sci. 2022 Dec 11;23(24):15706. doi: 10.3390/ijms232415706.
Understanding which intracellular signaling pathways are activated by manganese stress is crucial to decipher how metal overload compromise cellular integrity. Here, we unveil a role for oxidative and cell wall stress signaling in the response to manganese stress in yeast. We find that the oxidative stress transcription factor Yap1 protects cells against manganese toxicity. Conversely, extracellular manganese addition causes a rapid decay in Yap1 protein levels. In addition, manganese stress activates the MAPKs Hog1 and Slt2 (Mpk1) and leads to an up-regulation of the Slt2 downstream transcription factor target Rlm1. Importantly, Yap1 and Slt2 are both required to protect cells from oxidative stress in mutants impaired in manganese detoxification. Under such circumstances, Slt2 activation is enhanced upon Yap1 depletion suggesting an interplay between different stress signaling nodes to optimize cellular stress responses and manganese tolerance.
了解锰胁迫激活哪些细胞内信号通路对于解析金属过载如何破坏细胞完整性至关重要。在这里，我们揭示了氧化应激和细胞壁应激信号在酵母应对锰胁迫中的作用。我们发现，氧化应激转录因子 Yap1 可保护细胞免受锰毒性的侵害。相反，细胞外添加锰会导致 Yap1 蛋白水平迅速下降。此外，锰胁迫激活 MAPKs Hog1 和 Slt2（Mpk1），并导致 Slt2 下游转录因子靶标 Rlm1 的上调。重要的是，在锰解毒功能受损的突变体中，Yap1 和 Slt2 均有助于保护细胞免受氧化应激。在这种情况下，Yap1 缺失会增强 Slt2 的激活，这表明不同应激信号节点之间存在相互作用，以优化细胞应激反应和锰耐受性。
