Molecular control of iron-sensing in yeast.

酵母中铁感应的分子控制。

• 批准号: 238238-2010
• 负责人: Labbe, Simon
• 金额: $ 4.08万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=524255
• 关键词: Molecular; control; iron; sensing; yeast.

Title. Molecular control of iron-sensing in yeast. All eukaryotes require iron (Fe) for survival. The ability of this transition metal to exist in two redox states makes it essential at the active center of many enzymes and electron transporters. Paradoxically, the properties that make Fe essential in these reactions can also make it toxic under certain conditions. Excess Fe has the ability to unleash toxic oxygen radicals that can damage cellular components. Consequently, organisms must tightly regulate their internal Fe load, and respond appropriately by controlling Fe acquisition and compartmentalization to maintain homeostasis. The yeast Schizosaccharomyces pombe is an outstanding model system for understanding many aspects of eukaryotic cell growth, metabolism, and signal transduction. Studies of S. pombe have identified novel genes that function in the regulation of Fe transport and have revealed their existence and importance in other organisms. In response to high Fe, the Fep1 transcription factor represses the expression of a set of genes involved in the acquisition of Fe. Under Fe-limiting conditions, optimization of cellular Fe utilization is coordinated by the Php4 protein, which acts as a negative regulatory subunit of the CCAAT-binding factor and fosters repression of genes encoding Fe-using proteins. Despite these recent findings, little is known about the mechanisms by which Fep1 and Php4 respond to low or high Fe availability. Furthermore, we know little about the functional roles of the products of many Fep1/Php4 target genes (>40 unexplored genes). Overall, the proposed research will provide a better understanding of the molecular circuitry of Fe-dependent cellular processes, including Fe-sensing by Fep1 and Php4, and Fe-trafficking that relies on the vacuolar Fe transporter Abc3. The long-term objective of this program is to use this knowledge to better understand the molecular basis of Fe homeostasis and use the results to draw parallels with other living systems. The proposed work also promises an exceptional opportunity for the training of highly qualified personnel, making them highly valuable to the Canadian biotech sector and/or academic research community.

标题. 酵母铁敏感的分子调控。 所有的真核生物都需要铁（Fe）才能生存。 这种过渡金属以两种氧化还原状态存在的能力使其在许多酶和电子转运体的活性中心至关重要。 奇怪的是，使铁在这些反应中必不可少的性质也可能使其在某些条件下有毒。 过量的铁有能力释放有毒的氧自由基，可以破坏细胞成分。 因此，生物体必须严格调节其内部的铁负荷，并通过控制铁的获取和区室化来维持体内平衡。粟酒裂殖酵母是了解真核细胞生长、代谢和信号转导许多方面的杰出模型系统。 研究S。粟酒裂殖酵母已经确定了新的基因，在铁运输的调节功能，并揭示了它们的存在和重要性，在其他生物体。 在高铁，Fep 1转录因子抑制一组基因的表达参与收购铁。 在铁限制条件下，细胞铁利用率的优化是由Php 4蛋白协调的，Php 4蛋白作为CCAAT结合因子的负调控亚基，并促进对编码铁利用蛋白的基因的抑制。 尽管这些最近的研究结果，很少有人知道的机制，Fep 1和Php 4响应低或高铁的可用性。 此外，我们对许多Fep 1/Php 4靶基因（>40个未探索的基因）产物的功能作用知之甚少。 总体而言，拟议的研究将提供更好地了解铁依赖性细胞过程的分子电路，包括Fep 1和Php 4的铁传感，以及依赖于液泡铁转运蛋白Abc 3的铁运输。 该计划的长期目标是利用这些知识更好地了解铁稳态的分子基础，并利用结果与其他生命系统进行比较。 拟议的工作还承诺为培训高素质的人员提供一个特殊的机会，使他们对加拿大生物技术部门和/或学术研究界非常有价值。