Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Insights Into the Roles of the Sideroflexins / SLC56 Family in Iron Homeostasis and Iron-Sulfur Biogenesis

Version 1 : Received: 22 December 2020 / Approved: 23 December 2020 / Online: 23 December 2020 (10:40:15 CET)

A peer-reviewed article of this Preprint also exists.

Tifoun, N.; De las Heras, J.M.; Guillaume, A.; Bouleau, S.; Mignotte, B.; Le Floch, N. Insights into the Roles of the Sideroflexins/SLC56 Family in Iron Homeostasis and Iron-Sulfur Biogenesis. Biomedicines 2021, 9, 103. Tifoun, N.; De las Heras, J.M.; Guillaume, A.; Bouleau, S.; Mignotte, B.; Le Floch, N. Insights into the Roles of the Sideroflexins/SLC56 Family in Iron Homeostasis and Iron-Sulfur Biogenesis. Biomedicines 2021, 9, 103.

Journal reference: Biomedicines 2021, 9, 103
DOI: 10.3390/biomedicines9020103

Abstract

Sideroflexins (SLC56 family) are highly conserved multi-spanning transmembrane proteins inserted in the inner mitochondrial membrane in eukaryotes. Few data are available on their molecular function but, since their first description, they were thought to be metabolite transporters probably required for iron utilization inside the mitochondrion. Such as numerous mitochondrial transporters, sideroflexins remain poorly characterized. The prototypic member SFXN1 has been recently identified as the previously unknown mitochondrial transporter of serine. Nevertheless, pending questions on the molecular function of sideroflexins remain unsolved, especially their link with iron metabolism. Here, we review the current knowledge on sideroflexins, their presumed mitochondrial functions and the sparse - but growing - evidence linking sideroflexins to iron homeostasis and iron-sulfur cluster biogenesis. Since an imbalance in iron homeostasis can be detrimental at the cellular and organismal levels, we also investigate the relationship between sideroflexins, iron and physiological disorders. Investigating Sideroflexins’ functions constitutes an emerging research field of great interest and will certainly lead to main discoveries on mitochondrial physiopathology.

Keywords

sideroflexin; mitochondria; mitochondrial transporters; iron homeostasis; iron-sulfur cluster; heme biosynthesis; one-carbon metabolism; ferroptosis; ferritinophagy.

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