Iron is a vital micronutrient for all eukaryotes because it participates as a redox cofactor in multiple metabolic pathways, including lipid biosynthesis. In response to iron deficiency, the Saccharomyces cerevisiae iron-responsive transcription factor Aft1 accumulates in the nucleus and activates a set of genes that promote iron acquisition at the cell surface. In this study, we report that yeast cells lacking the transcription factor Mga2, which promotes the expression of the iron-dependent Δ9-fatty acid desaturase Ole1, display a defect in the activation of the iron regulon during the adaptation to iron limitation. Supplementation with exogenous unsaturated fatty acids (UFAs) or OLE1 expression rescues the iron regulon activation defect of mga2Δ cells. These observations and fatty acid measurements suggest that the mga2Δ defect in iron regulon expression is due to low UFA levels. Subcellular localization studies reveal that low UFAs cause a mislocalization of Aft1 protein to the vacuole upon iron deprivation that prevents its nuclear accumulation. These results indicate that Mga2 and Ole1 are essential to maintain the UFA levels required for Aft1-dependent activation of the iron regulon in response to iron deficiency, and directly connect the biosynthesis of fatty acids to the response to iron depletion.

中文翻译：

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酵母细胞的脂质组成调节对铁缺乏的反应。

铁是所有真核生物的重要微量营养素，因为铁作为氧化还原辅因子参与了多种代谢途径，包括脂质的生物合成。响应铁缺乏症，酿酒酵母铁响应转录因子Aft1积累在细胞核中，并激活一组促进细胞表面铁吸收的基因。在这项研究中，我们报告酵母细胞缺乏转录因子Mga2，该转录因子可促进铁依赖性Δ9-脂肪酸去饱和酶Ole1的表达，在适应铁限制的过程中在铁调节子的激活中显示缺陷。补充外源性不饱和脂肪酸（UFA）或OLE1表达可挽救mga2Δ细胞的铁调节子激活缺陷。这些观察结果和脂肪酸测量结果表明，铁调节子表达中的mga2Δ缺陷是由于低UFA水平引起的。亚细胞定位研究表明，低UFA会在铁缺乏时导致Aft1蛋白向液泡错位，从而阻止其核积累。这些结果表明，Mga2和Ole1对维持响应铁缺乏的Aft1依赖性铁调节子的Aft1活化所需的UFA水平至关重要，并将脂肪酸的生物合成与对铁耗竭的响应直接相关。