Ramos-Alonso Lucía, Romero Antonia María, Martínez-Pastor María Teresa, Puig Sergi
Departamento de Biotecnología, Instituto de Agroquímica y Tecnología de Alimentos (IATA), Consejo Superior de Investigaciones Científicas (CSIC), Valencia, Spain.
Departamento de Bioquímica y Biología Molecular, Universitat de València, Valencia, Spain.
Front Microbiol. 2020 Sep 9;11:582830. doi: 10.3389/fmicb.2020.582830. eCollection 2020.
Iron is an essential micronutrient for all eukaryotic organisms because it participates as a redox cofactor in many cellular processes. However, excess iron can damage cells since it promotes the generation of reactive oxygen species. The budding yeast has been used as a model organism to study the adaptation of eukaryotic cells to changes in iron availability. Upon iron deficiency, yeast utilizes two transcription factors, Aft1 and Aft2, to activate the expression of a set of genes known as the iron regulon, which are implicated in iron uptake, recycling and mobilization. Moreover, Aft1 and Aft2 activate the expression of Cth2, an mRNA-binding protein that limits the expression of genes encoding for iron-containing proteins or that participate in iron-using processes. Cth2 contributes to prioritize iron utilization in particular pathways over other highly iron-consuming and non-essential processes including mitochondrial respiration. Recent studies have revealed that iron deficiency also alters many other metabolic routes including amino acid and lipid synthesis, the mitochondrial retrograde response, transcription, translation and deoxyribonucleotide synthesis; and activates the DNA damage and general stress responses. At high iron levels, the yeast Yap5, Msn2, and Msn4 transcription factors activate the expression of a vacuolar iron importer called Ccc1, which is the most important high-iron protecting factor devoted to detoxify excess cytosolic iron that is stored into the vacuole for its mobilization upon scarcity. The complete sequencing and annotation of many yeast genomes is starting to unveil the diversity and evolution of the iron homeostasis network in this species.
铁是所有真核生物必需的微量营养素，因为它作为氧化还原辅助因子参与许多细胞过程。然而，过量的铁会损害细胞，因为它会促进活性氧的产生。芽殖酵母已被用作模式生物来研究真核细胞对铁可用性变化的适应性。在缺铁时，酵母利用两种转录因子Aft1和Aft2来激活一组被称为铁调节子的基因的表达，这些基因与铁的摄取、循环利用和动员有关。此外，Aft1和Aft2激活Cth2的表达，Cth2是一种mRNA结合蛋白，它限制编码含铁蛋白或参与铁利用过程的基因的表达。Cth2有助于在特定途径中优先利用铁，而不是其他高铁消耗和非必需过程，包括线粒体呼吸。最近的研究表明，缺铁还会改变许多其他代谢途径，包括氨基酸和脂质合成、线粒体逆行反应、转录、翻译和脱氧核糖核苷酸合成；并激活DNA损伤和一般应激反应。在高铁水平下，酵母Yap5、Msn2和Msn4转录因子激活一种名为Ccc1的液泡铁导入蛋白的表达，Ccc1是最重要的高铁保护因子，致力于将多余的胞质铁解毒，这些铁被储存到液泡中，以便在缺乏时进行动员。许多酵母基因组的完整测序和注释开始揭示该物种中铁稳态网络的多样性和进化。
