SFXN1 是一种线粒体丝氨酸转运体，对于一碳代谢是必需的。
SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism.
机构信息
Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA.
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
出版信息
Science. 2018 Nov 16;362(6416). doi: 10.1126/science.aat9528.
One-carbon metabolism generates the one-carbon units required to synthesize many critical metabolites, including nucleotides. The pathway has cytosolic and mitochondrial branches, and a key step is the entry, through an unknown mechanism, of serine into mitochondria, where it is converted into glycine and formate. In a CRISPR-based genetic screen in human cells for genes of the mitochondrial pathway, we found sideroflexin 1 (SFXN1), a multipass inner mitochondrial membrane protein of unclear function. Like cells missing mitochondrial components of one-carbon metabolism, those null for SFXN1 are defective in glycine and purine synthesis. Cells lacking SFXN1 and one of its four homologs, SFXN3, have more severe defects, including being auxotrophic for glycine. Purified SFXN1 transports serine in vitro. Thus, SFXN1 functions as a mitochondrial serine transporter in one-carbon metabolism.
一碳代谢生成合成许多关键代谢物所需的一碳单位，包括核苷酸。该途径有细胞质和线粒体分支，关键步骤是丝氨酸通过未知机制进入线粒体，在那里它转化为甘氨酸和甲酸盐。在人类细胞中基于 CRISPR 的线粒体途径基因的遗传筛选中，我们发现了铁氧还蛋白 1（SFXN1），一种功能不明的多跨线粒体内膜蛋白。与缺失一碳代谢线粒体成分的细胞一样，SFXN1 缺失的细胞在甘氨酸和嘌呤合成中存在缺陷。缺乏 SFXN1 和它的四个同源物之一 SFXN3 的细胞有更严重的缺陷，包括对甘氨酸的营养缺陷性。纯化的 SFXN1 在体外转运丝氨酸。因此，SFXN1 在一碳代谢中作为线粒体丝氨酸转运蛋白发挥作用。
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