Iron uptake proteins in algae and the role of Iron Starvation-Induced Proteins (ISIPs)

Iron is one of the most abundant elements on Earth, and it is essential for life. Despite the abundance of iron, its chemistry leads to very limited bioavailability, which has resulted in the evolution of a wide range of proteins involved in uptake and scavenging. However, because high intracellular concentrations of iron are toxic, iron homeostasis is essential for every organism. Approximately 30–40% of the ocean’s surface is characterized by very low chlorophyll concentrations and high concentrations of nitrate and phosphate. These High Nutrient-Low Chlorophyll (HNLC) regions are also characterized by low concentrations of iron, and studies on low-iron adapted diatom strains revealed the presence of iron starvation-induced proteins (ISIP), a group of unrelated novel proteins that are strongly up-regulated under iron limitation. First functional characterizations show that some of these ISIP proteins are involved in iron uptake. Here, we compare iron-uptake/storage proteins from 15 different algal species demonstrating that some well-characterized uptake proteins such as Natural Resistance Associated Macrophage Proteins (NRAMP) or the iron transporter1 (FTR1)-like permease show high similarities throughout the 15 algal species, while others such as Zinc-Regulated Transporter (ZRT)- and Iron-Regulated Transporter (IRT)-like proteins (ZIP) have a higher diversity amongst the algae analysed here. The focus of this review is ISIP proteins, which are distinct from ZIP, NRAMP and FTR1 permeases. ISIP2 proteins are transferrin-like proteins involved in Fe3+ uptake and ISIP1 is responsible for endocytosis of siderophore-bound iron. Additionally, in-silico analysis, combined with our localization study in a marine diatom, suggests that ISIP3 acts as an iron storage protein. Overall, our analysis concludes that marine algae combine iron uptake strategies widespread in other organisms, with algal-specific ISIPs as additional proteins for the utilization of diverse iron pools, thereby securing their success in iron-poor regions.铁是地球上丰度最高的元素之一，同时也是生命活动所必需的营养元素。尽管铁的自然储量极为丰富，但其化学特性导致其生物可利用性极低，这推动演化出了一系列参与铁摄取与清除的蛋白质家族。然而，由于细胞内铁浓度过高会产生毒性，铁稳态（iron homeostasis）对所有生物体都至关重要。 全球约30%~40%的海洋表层水域呈现出极低的叶绿素浓度与较高的硝酸盐、磷酸盐浓度，这类高营养盐低叶绿素（High Nutrient-Low Chlorophyll, HNLC）区域同时也存在铁浓度偏低的特征。针对低铁适应性硅藻菌株的研究发现了铁饥饿诱导蛋白（iron starvation-induced proteins, ISIP）——这是一类结构无关的新型蛋白质，在铁限制条件下会被显著上调。 初步功能表征研究表明，部分ISIP蛋白参与铁摄取过程。本研究对15种不同藻类的铁摄取/储存蛋白进行了比较分析，结果显示，部分已被充分研究的摄取蛋白，如天然抗性相关巨噬细胞蛋白（Natural Resistance Associated Macrophage Proteins, NRAMP）或铁转运蛋白1（iron transporter1, FTR1）类通透酶，在这15种藻类中具有高度相似性；而另一些蛋白，如锌调控转运蛋白（Zinc-Regulated Transporter, ZRT）与铁调控转运蛋白（Iron-Regulated Transporter, IRT）类蛋白（ZIP家族），在本次分析的藻类中则表现出更高的多样性。 本综述的核心研究对象为ISIP蛋白，它们与ZIP、NRAMP及FTR1通透酶存在显著区别。ISIP2属于类运铁蛋白，参与Fe³+的摄取过程；ISIP1则负责介导结合了铁载体的铁的内吞作用。此外，结合我们在海洋硅藻中的定位研究所开展的计算机模拟（in silico）分析表明，ISIP3可作为铁储存蛋白。 综合来看，本分析表明海洋藻类整合了其他生物体中广泛存在的铁摄取策略，并通过藻类特异性的ISIP蛋白作为额外的铁利用工具，以适配多样化的铁池环境，从而保障了它们在低铁水域中的生存优势。