SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism
Name
nihms-999380.pdf
Description
Accepted version
Size
1.71 MB
Format
Adobe PDF
Checksum (MD5)
147d08caca5d7302a73a21c6ddb60092
Author(s)
Kory, Nora
Wyant, Gregory A.
Prakash, Gyan
De Bos, Jelmi uit
Pacold, Michael E.
Chan, Sze Ham
Lewis, Caroline A.
Wang, Tim
Keys, Heather R.
Sabatini, David M.
Date Issued
November 2018
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Kory, Nora et al. "SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism." Science 362 (2018): aat9528 © 2018 The Authors
Version
Author's final manuscript
Abstract
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.
MIT Department
Whitehead Institute for Biomedical Research
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1126/SCIENCE.AAT9528
