2.A.54.1.1
Mitochondrial serine (and possibly cystine and alanine) carrier, Sideroflexin-1 (SFXN1; SLC56A1), of 322 aas and probably 5 TMSs (Kory et al. 2018). This system is believed to be required for one-carbon metabolism because serine is converted into glycine and formate in the mitochondrion. SFXN1, an integral inner mitochondrial membrane (IMM) protein with an uneven number of transmembrane domains, is a TIM22 complex substrate. An SFXN1 deficiency leads to mitochondrial respiratory chain impairments, the most detrimental being to complex III (CIII) biogenesis, activity, and assembly, compromising coenzyme Q levels (Acoba et al. 2021). The CIII dysfunction is independent of one-carbon metabolism, the known primary role for SFXN1 as a mitochondrial serine transporter. Instead, SFXN1 supports CIII function by participating in heme and alpha-ketoglutarate metabolism. Thus, SFXN1-based amino acid transport impacts mitochondrial and cellular metabolic efficiency in multiple ways. The TIM22 complex mediates the import of sideroflexins which transport L- and D-serine and other amino acids, and it is therefore required for efficient mitochondrial one-carbon metabolism (Jackson et al. 2021). SFXN1 interacts with ATAD3 and HSD10, both associated with neurological disorders (Tifoun et al. 2022).