Aluminium, gallium, and indium are group 13 metals with similar chemical and physical properties. While aluminium is one of the most abundant elements in the Earth's crust, gallium and indium are present only in trace amounts. However, the increased use of the latter metals in novel technologies may result in increased human and environmental exposure. There is mounting evidence that these metals are toxic, but the underlying mechanisms remain poorly understood. Likewise, little is known about how cells protect themselves from these metals. Aluminium, gallium, and indium are relatively insoluble at neutral pH, and here we show that they precipitate in yeast culture medium at acidic pH as metal-phosphate species. Despite this, the dissolved metal concentrations are sufficient to induce toxicity in the yeast Saccharomyces cerevisiae. By chemical-genomic profiling of the S. cerevisiae gene deletion collection, we identified genes that maintain growth in the presence of the three metals. We found both shared and metal-specific genes that confer resistance. The shared gene products included functions related to calcium metabolism and Ire1/Hac1-mediated protection. Metal-specific gene products included functions in vesicle-mediated transport and autophagy for aluminium, protein folding and phospholipid metabolism for gallium, and chorismate metabolic processes for indium. Many of the identified yeast genes have human orthologues involved in disease processes. Thus, similar protective mechanisms may act in yeast and humans. The protective functions identified in this study provide a basis for further investigations into toxicity and resistance mechanisms in yeast, plants, and humans.

中文翻译：

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化学基因组分析可识别保护酵母免受铝、镓和铟毒性的基因。

铝、镓和铟属于第 13 族金属，具有相似的化学和物理性质。虽然铝是地壳中最丰富的元素之一，但镓和铟的含量仅为微量。然而，在新技术中增加使用后一种金属可能会导致人类和环境暴露增加。越来越多的证据表明这些金属有毒，但其潜在机制仍知之甚少。同样，人们对细胞如何保护自己免受这些金属的侵害知之甚少。铝、镓和铟在中性 pH 值下相对难溶，在这里我们证明它们在酸性 pH 值下在酵母培养基中以金属磷酸盐形式沉淀。尽管如此，溶解的金属浓度足以在酿酒酵母中诱导毒性。通过对酿酒酵母基因缺失集合进行化学基因组分析，我们鉴定了在三种金属存在下维持生长的基因。我们发现了具有抗性的共享基因和金属特异性基因。共享的基因产物包括与钙代谢和 Ire1/Hac1 介导的保护相关的功能。金属特异性基因产物包括铝的囊泡介导的运输和自噬、镓的蛋白质折叠和磷脂代谢以及铟的分支酸代谢过程中的功能。许多已鉴定的酵母基因都具有参与疾病过程的人类直系同源物。因此，类似的保护机制可能在酵母和人类中发挥作用。本研究确定的保护功能为进一步研究酵母、植物、