Insights on the endogenous labile iron pool binding properties

IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
André Luís Condeles, Gabriel Simonetti da Silva, Maria Beatriz Braghetto Hernandes, José Carlos Toledo Junior
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Abstract

Under normal physiological conditions, the endogenous Labile Iron Pool (LIP) constitutes a ubiquitous, dynamic, tightly regulated reservoir of cellular ferrous iron. Furthermore, LIP is loaded into new apo-iron proteins, a process akin to the activity of metallochaperones. Despite such importance on iron metabolism, the LIP identity and binding properties have remained elusive. We hypothesized that LIP binds to cell constituents (generically denoted C) and forms an iron complex termed CLIP. Combining this binding model with the established Calcein (CA) methodology for assessing cytosolic LIP, we have formulated an equation featuring two experimentally quantifiable parameters (the concentrations of the cytosolic free CA and CA and LIP complex termed CALIP) and three unknown parameters (the total concentrations of LIP and C and their thermodynamic affinity constant Kd). The fittings of cytosolic CALIP × CA concentrations data encompassing a few cellular models to this equation with floating unknown parameters were successful. The computed adjusted total LIP (LIPT) and C (CT) concentrations fall within the sub-to-low micromolar range while the computed Kd was in the 10−2 µM range for all cell types. Thus, LIP binds and has high affinity to cellular constituents found in low concentrations and has remarkably similar properties across different cell types, shedding fresh light on the properties of endogenous LIP within cells.

Abstract Image

Abstract Image

洞察内源性易溶铁池的结合特性
在正常生理条件下,内源性易损铁池(LIP)是一个无处不在、动态的、受到严格调控的细胞亚铁库。此外,LIP 还能被加载到新的载铁蛋白中,这一过程类似于金属合子的活性。尽管 LIP 在铁代谢中具有如此重要的作用,但其身份和结合特性却一直难以捉摸。我们假设 LIP 与细胞成分(通称为 C)结合,并形成一种称为 CLIP 的铁复合物。将这一结合模型与评估细胞膜 LIP 的钙黄绿素(Calcein,CA)成熟方法相结合,我们制定了一个方程,其中包含两个实验量化参数(细胞膜游离 CA 和 CA 与 LIP 复合物(称为 CALIP)的浓度)和三个未知参数(LIP 和 C 的总浓度及其热力学亲和力常数 Kd)。将一些细胞模型的细胞质 CALIP × CA 浓度数据与该方程的浮动未知参数拟合成功。计算出的调整后总 LIP(LIPT)和 C(CT)浓度在亚微摩尔到低微摩尔范围内,而计算出的 Kd 在所有细胞类型的 10-2 µM 范围内。因此,LIP 与低浓度的细胞成分结合并具有很高的亲和力,而且在不同类型的细胞中具有非常相似的特性,这为我们揭示细胞内源性 LIP 的特性提供了新的思路。
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来源期刊
Biometals
Biometals 生物-生化与分子生物学
CiteScore
5.90
自引率
8.60%
发文量
111
审稿时长
3 months
期刊介绍: BioMetals is the only established journal to feature the important role of metal ions in chemistry, biology, biochemistry, environmental science, and medicine. BioMetals is an international, multidisciplinary journal singularly devoted to the rapid publication of the fundamental advances of both basic and applied research in this field. BioMetals offers a forum for innovative research and clinical results on the structure and function of: - metal ions - metal chelates, - siderophores, - metal-containing proteins - biominerals in all biosystems. - BioMetals rapidly publishes original articles and reviews. BioMetals is a journal for metals researchers who practice in medicine, biochemistry, pharmacology, toxicology, microbiology, cell biology, chemistry, and plant physiology who are based academic, industrial and government laboratories.
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