NeuroMolecular Medicine

, Volume 21, Issue 3, pp 314–321 | Cite as

Sideroflexin 3 is a Mitochondrial Protein Enriched in Neurons

  • Aileen Rivell
  • Ronald S. Petralia
  • Ya-Xian Wang
  • Mark P. Mattson
  • Pamela J. YaoEmail author
Original Paper


Sideroflexin 1 (Sfxn1) is a mitochondrial serine transporter involved in one-carbon metabolism in blood and cancer cell lines. The expression of other Sfxn homologs varies across tissues implying that each homolog may have tissue-specific functions. RNA databases suggest that among the Sfxns, Sfxn3 may have a specific function in the brain. Here, we systematically analyzed the level, cellular distribution, and subcellular localization of Sfxn3 protein in the developing and adult rodent brain. We found that, in the cortex and hippocampus, Sfxn3 protein level is low at birth but increases during development and remains at a high level in the mature brains. Similarly, in cultured hippocampal neurons, Sfxn3 protein level is low in young neurons but increases as neurons mature. Sfxn3 protein level is much higher in neurons than in astrocytes. Within neurons, Sfxn3 localizes to mitochondria in all major neuronal compartments. Our results establish that Sfxn3 is a mitochondrial protein enriched in neurons wherein it is developmentally expressed. These findings provide a foundation for future research aimed at understanding the functions of Sfxn3 and one-carbon metabolism in neurons.


Sideroflexin Mitochondria Brain Neuron One-carbon metabolism 



We thank Dr. Fred E. Indig for assistance in confocal Airyscan imaging. We thank Drs. Lin Lin and Dax Hoffman for mouse tissue for immunogold labeling. This study was supported by the Intramural Research Programs of the National Institutes of Health, National Institute on Aging; and the National Institutes of Health, National Institute on Deafness and Other Communication Disorders. The Advanced Imaging Core code is ZIC DC000081.

Supplementary material

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Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2019

Authors and Affiliations

  1. 1.Laboratory of NeurosciencesNIA/NIH Biomedical Research CenterBaltimoreUSA
  2. 2.Advanced Imaging CoreNIDCD/NIHBethesdaUSA

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