SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism.
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.
|Year of Publication||
2018 Nov 16
|PubMed Central ID||
R01 CA103866 / CA / NCI NIH HHS / United States
S10 OD020142 / OD / NIH HHS / United States
T32 GM007287 / GM / NIGMS NIH HHS / United States
HHMI / Howard Hughes Medical Institute / United States
R37 AI047389 / AI / NIAID NIH HHS / United States
R01 CA129105 / CA / NCI NIH HHS / United States