Cell Signalling in Yeast Unit, Department of Basic Medical Sciences, Institut de Recerca Biomèdica de Lleida (IRBLleida), University of Lleida, 25198 Lleida, Spain.
Department of Microbiology and Parasitology, Faculty of Pharmacy, University Complutense de Madrid, IRYCIS, 28040 Madrid, Spain.
Biochim Biophys Acta Mol Cell Res. 2021 Apr;1868(5):118974. doi: 10.1016/j.bbamcr.2021.118974. Epub 2021 Feb 4.
Iron is an essential element for life. Cells develop mechanisms to tightly regulate its homeostasis, in order to avoid abnormal accumulation and the consequent cell toxicity. In budding yeast, the high affinity iron regulon is under the control of the transcription factor Aft1. We present evidence demonstrating that the MAPK Slt2 of the cell wall integrity pathway (CWI), phosphorylates and negatively regulates Aft1 activity upon the iron depletion signal, both in fermentative or respiratory conditions. The lack of Slt2 provokes Aft1 dysfunction leading to a shorter chronological life span. The signal of iron scarcity is not transmitted to Slt2 through other signalling pathways such as TOR1, PKA, SNF1 or TOR2/YPK1. The observation that Slt2 physically binds Aft1 rather suggests a direct regulation.
铁是生命所必需的元素。细胞会发展出各种机制来严格调节铁的稳态，以避免异常积累和随之产生的细胞毒性。在 budding yeast 中，高亲和力的铁调节因子受转录因子 Aft1 的控制。我们提供的证据表明，细胞壁完整性途径（CWI）中的 MAPK Slt2 在铁耗竭信号下，无论是在发酵还是呼吸条件下，磷酸化并负调控 Aft1 的活性。缺乏 Slt2 会导致 Aft1 功能障碍，从而缩短酵母的chronological 寿命。铁缺乏的信号不会通过其他信号通路（如 TOR1、PKA、SNF1 或 TOR2/YPK1）传递给 Slt2。观察到 Slt2 与 Aft1 直接结合，这表明可能存在直接调控。
