Xue Yong, Schmollinger Stefan, Attar Narsis, Campos Oscar A, Vogelauer Maria, Carey Michael F, Merchant Sabeeha S, Kurdistani Siavash K
From the Department of Biological Chemistry.
Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Huaihai Institute of Technology, Lianyungang 222005, China.
J Biol Chem. 2017 Aug 11;292(32):13197-13204. doi: 10.1074/jbc.M117.784249. Epub 2017 Jun 21.
The endoplasmic reticulum (ER)-mitochondria encounter structure (ERMES) is a protein complex that physically tethers the two organelles to each other and creates the physical basis for communication between them. ERMES functions in lipid exchange between the ER and mitochondria, protein import into mitochondria, and maintenance of mitochondrial morphology and genome. Here, we report that ERMES is also required for iron homeostasis. Loss of ERMES components activates an Aft1-dependent iron deficiency response even in iron-replete conditions, leading to accumulation of excess iron inside the cell. This function is independent of known ERMES roles in calcium regulation, phospholipid biosynthesis, or effects on mitochondrial morphology. A mutation in the vacuolar protein sorting 13 () gene that rescues the glycolytic phenotype of ERMES mutants suppresses the iron deficiency response and iron accumulation. Our findings reveal that proper communication between the ER and mitochondria is required for appropriate maintenance of cellular iron levels.
内质网-线粒体接触结构（ERMES）是一种蛋白质复合物，它在物理上使这两个细胞器相互连接，并为它们之间的通讯创造了物理基础。ERMES在内质网和线粒体之间的脂质交换、蛋白质导入线粒体以及维持线粒体形态和基因组方面发挥作用。在此，我们报告ERMES对于铁稳态也是必需的。即使在铁充足的条件下，ERMES组分的缺失也会激活Aft1依赖性的缺铁反应，导致细胞内过量铁的积累。该功能独立于ERMES在钙调节、磷脂生物合成或对线粒体形态的影响等已知作用。液泡蛋白分选13（）基因中的一个突变可挽救ERMES突变体的糖酵解表型，该突变抑制了缺铁反应和铁积累。我们的研究结果表明，内质网和线粒体之间的适当通讯对于细胞铁水平的适当维持是必需的。
