Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

A High-throughput Search for SFXN1 Physical Partners Led to the Identification of ATAD3, HSD10, TIM50 and Subunits of Respiratory Complexes

Nesrine Tifoun
,
Mourad Bekhouche
ORCID logo ,
José M. De Las Heras
,
Arnaud Guillaume
,
Sylvina Bouleau
,
Isabelle Guénal
ORCID logo ,
Bernard Mignotte
,
Nathalie Le Floch
* ORCID logo
Version 1 : Received: 29 July 2022 / Approved: 2 August 2022 / Online: 2 August 2022 (07:46:32 CEST)

A peer-reviewed article of this Preprint also exists.

Tifoun, N.; Bekhouche, M.; De las Heras, J.M.; Guillaume, A.; Bouleau, S.; Guénal, I.; Mignotte, B.; Le Floch, N. A High-Throughput Search for SFXN1 Physical Partners Led to the Identification of ATAD3, HSD10 and TIM50. Biology 2022, 11, 1298. Tifoun, N.; Bekhouche, M.; De las Heras, J.M.; Guillaume, A.; Bouleau, S.; Guénal, I.; Mignotte, B.; Le Floch, N. A High-Throughput Search for SFXN1 Physical Partners Led to the Identification of ATAD3, HSD10 and TIM50. Biology 2022, 11, 1298.

Abstract

Sideroflexins (SFXN) are evolutionarily conserved mitochondrial carriers belonging to the SCL56 family. Until recently, the metabolites transported by SFXN were unknown and they were thought to be transporters of a metabolite involved in iron homeostasis. SFXN1 is now known as the mitochondrial serine transporter. Because little is known about SFXN1 interactome, we launched a high-throughput search of SFXN1 binding partners with the aim to better understand its mitochondrial functions. Using a large-scale identification of SFXN1 physical partners based on co-immunoprecipitation followed by shotgun mass spectrometry (coIP-MS), we identified 96 putative SFXN1 interactants in the MCF7 human cell line. Our in-silico analysis of the SFXN1 interactome highlights biological processes linked to mitochondrial organization, electron transport chain and transmembrane transport. Among SFXN1 potential physical partners, ATAD3A and 17-HSD10, two proteins associated with neurological disorders and neurodegeneration, were further confirmed as interactants using different human cell lines. Further work will be needed to investigate the significance of these interactions in neurological disorders.

Keywords

sideroflexin; SFXN1; mitochondria; ATAD3A; 17beta-HSD10; TIM50

Subject

Biology and Life Sciences, Endocrinology and Metabolism

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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