Sideroflexin 4 is a complex I assembly factor that interacts with the MCIA complex and is required for the assembly of the ND2 module

Jackson, Thomas Daniel; Crameri, Jordan J.; Muellner-Wong, Linden; Frazier, Ann E; Palmer, Catherine S; Formosa, Luke E.; Hock, Daniella H; Fujihara, Kenji M.; Stait, Tegan; Sharpe, Alice J.; Thorburn, David R.; Ryan, Michael; Stroud, David A.; Stojanovski, Diana

doi:10.1073/pnas.2115566119

Cited by 18 publications

(14 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Homologs of MTCH2 are present in metazoan peroxisomes and its orthologs are found throughout holozoa, suggesting that the MTCH2 family has co-opted the SLC25 transporter fold to function in diverse biological membranes. This type of functional divergence has been previously described for SFXN4 and ATP13A1, both transporter family proteins that have evolved biogenesis or dislocase functions, respectively (18, 24, 39).…”

Section: Main Textsupporting

confidence: 61%

MTCH2 is a mitochondrial outer membrane protein insertase

Guna

Stevens

Inglis

et al. 2022

Preprint

View full text Add to dashboard Cite

In the mitochondrial outer membrane, tail-anchored (TA) proteins play critical roles in cytoplasmic-mitochondrial communication. Using genome-wide CRISPRi screens, we identify factors involved in mitochondrial TA biogenesis in human cells. We show that MTCH2, and its paralog MTCH1, are required for insertion of biophysically diverse mitochondrial TAs, but not outer membrane b-barrel proteins. In a reconstituted system, purified MTCH2 is sufficient to mediate insertion into proteoliposomes. Functional and mutational studies reveal that MTCH2 uses membrane-embedded hydrophilic residues to function as a gatekeeper for outer membrane protein biogenesis, controlling mislocalization of TAs into the endoplasmic reticulum and the sensitivity of leukemia cells to apoptosis. Our identification of MTCH2 as an insertase provides a mechanistic explanation for the diverse phenotypes and disease states associated with MTCH2 dysfunction.

show abstract

Section: Main Textsupporting

confidence: 61%

MTCH2 is a mitochondrial outer membrane protein insertase

Guna

Stevens

Inglis

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…The SFXN1 physical interactors identified here suggested that SFXN1 could be in the vicinity of respiratory complexes I and IV. SFXN4 was recently shown to act as an assembly factor for complex I, interacting with the mitochondrial complex I intermediate assembly (MCIA), which contains TMEM126B [ 62 ]. Amongst the FXN1 partners identified in this study, TMEM126A and TIMMDC1 are two complex I assembly factors interacting with MCIA [ 63 , 64 ].…”

Section: Discussionmentioning

confidence: 99%

A High-Throughput Search for SFXN1 Physical Partners Led to the Identification of ATAD3, HSD10 and TIM50

Tifoun

Bekhouche

Heras

et al. 2022

Biology

View full text Add to dashboard Cite

Sideroflexins (SFXN, SLC56) are a family of evolutionarily conserved mitochondrial carriers potentially involved in iron homeostasis. One member of the SFXN family is SFXN1, recently identified as a human mitochondrial serine transporter. However, little is known about the SFXN1 interactome, necessitating a high-throughput search to better characterize SFXN1 mitochondrial functions. Via co-immunoprecipitation followed by shotgun mass spectrometry (coIP-MS), we identified 96 putative SFXN1 interactors in the MCF7 human cell line. Our in silico analysis of the SFXN1 interactome highlights biological processes linked to mitochondrial organization, electron transport chains and transmembrane transport. Among the potential physical partners, ATAD3A and 17β-HSD10, two proteins associated with neurological disorders, were confirmed using different human cell lines. Nevertheless, further work will be needed to investigate the significance of these interactions.

show abstract

“…SFXN1 physical interactants identified here permit to link SFXN1 to complex I and complex IV suggesting that SFXN1 is in the vicinity of respiratory complexes. SFXN4 was recently shown to act as an assembly factor for the complex I interacting with the mitochondrial complex I intermediate assembly (MCIA) which contains TMEM126B [60]. Amongst SFXN1 partners we identified, TMEM126A and TIMMDC1 are two complex I assembly factors interacting with MCIA [61,62].…”

Section: Discussionmentioning

confidence: 90%

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

Tifoun¹,

Bekhouche²,

Heras³

et al. 2022

Preprint

View full text Add to dashboard Cite

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.

show abstract

Sideroflexin 4 is a complex I assembly factor that interacts with the MCIA complex and is required for the assembly of the ND2 module

Cited by 18 publications

References 37 publications

MTCH2 is a mitochondrial outer membrane protein insertase

MTCH2 is a mitochondrial outer membrane protein insertase

A High-Throughput Search for SFXN1 Physical Partners Led to the Identification of ATAD3, HSD10 and TIM50

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

Contact Info

Product

Resources

About