Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Institute for Experimental Molecular Imaging (ExMI), RWTH Aachen University Hospital, Forckenbeckstr. 55, Aachen 52074, Germany.
Metallomics. 2023 Aug 1;15(8). doi: 10.1093/mtomcs/mfad039.
Despite their similar physicochemical properties, recent studies have demonstrated that lanthanides can display different biological behaviors. Hence, the lanthanide series can be divided into three parts, namely early, mid, and late lanthanides, based on their interactions with biological systems. In particular, the late lanthanides demonstrate distinct, but poorly understood biological activity. In the current study, we employed genome-wide functional screening to help understand biological effects of exposure to Yb(III) and Lu(III), which were selected as representatives of the late lanthanides. As a model organism, we used Saccharomyces cerevisiae, since it shares many biological functions with humans. Analysis of the functional screening results indicated toxicity of late lanthanides is consistent with disruption of vesicle-mediated transport, and further supported a role for calcium transport processes and mitophagy in mitigating toxicity. Unexpectedly, our analysis suggested that late lanthanides target proteins with SH3 domains, which may underlie the observed toxicity. This study provides fundamental insights into the unique biological chemistry of late lanthanides, which may help devise new avenues toward the development of decorporation strategies and bio-inspired separation processes.
尽管它们具有相似的物理化学性质，但最近的研究表明，镧系元素可以表现出不同的生物行为。因此，根据它们与生物系统的相互作用，镧系元素可以分为三部分，即早期、中期和晚期镧系元素。特别是，晚期镧系元素表现出独特但尚未完全理解的生物活性。在本研究中，我们采用全基因组功能筛选来帮助理解 Yb(III)和 Lu(III)暴露的生物学效应，这两种元素被选为晚期镧系元素的代表。我们选择酿酒酵母作为模式生物，因为它与人类有许多生物学功能。功能筛选结果的分析表明，晚期镧系元素的毒性与囊泡介导的运输中断一致，并进一步支持钙运输过程和线粒体自噬在减轻毒性中的作用。出乎意料的是，我们的分析表明，晚期镧系元素靶向具有 SH3 结构域的蛋白质，这可能是观察到的毒性的基础。这项研究为晚期镧系元素独特的生物化学提供了基本的见解，这可能有助于设计新的去金属策略和仿生分离过程。
