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

TD Jackson; JJ Crameri; L Muellner-Wong; AE Frazier; CS Palmer; LE Formosa; DH Hock; KM Fujihara; T Stait; AJ Sharpe; DR Thorburn; MT Ryan; DA Stroud; D Stojanovski

Journal article

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

TD Jackson, JJ Crameri, L Muellner-Wong, AE Frazier, CS Palmer, LE Formosa, DH Hock, KM Fujihara, T Stait, AJ Sharpe, DR Thorburn, MT Ryan, DA Stroud, D Stojanovski

Proceedings of the National Academy of Sciences of the United States of America | Published : 2022

DOI: 10.1073/pnas.2115566119

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Abstract

Sideroflexins (SFXNs) comprise a family of five paralogous proteins (SFXN1–5) in metazoan species. SFXN1/2/3 function as mitochondrial serine transporters and are required for efficient mitochondrial one-carbon (1C) metabolism. SFXN4 is evolutionarily divergent, and mutations in SFXN4 give rise to mitochondrial disease, pointing to a distinct function of this protein in mitochondrial biology. Using a combination of genome editing, interaction studies, and quantitative proteomics, we show that loss of SFXN4 leads to an isolated complex I assembly defect and that SFXN4 interacts with the core components of the mitochondrial complex I intermediate assembly (MCIA) complex. Our findings suggest t..

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University of Melbourne Researchers

Ann Frazier Author

Catherine Palmer Author

Daniella Hock Author

David Thorburn Author

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Grants

Awarded by State Government of Victoria

Funding Acknowledgements

We acknowledge support from the Mito Foundation to Stojanovski Lab (Incubator and Booster Grant) . T.D.J., J.J.C., and K.M.F. are sup-ported by Australian Government Research Training Program scholarships. D.H.H. is supported by a Melbourne International Research Scholarship. T.D.J., J.J.C., and D.H.H. are supported by Mito Foundation PhD Top-Up scholarships. We acknowledge funding from the Australian National Health and Medical Research Council (NHMRC Project Grant GNT1140906 to D.A.S. and M.T.R.; GNT1107094 to D.R.T.; NHMRC Fellowship 1140851 to D.A.S.; 1155244 to D.R.T.; EL1 Investigator Grant APP2010149 to L.E.F.) . We thank the Bio21 Mass Spectrometry and Proteomics Facility for the provision of instrumentation, train-ing, and technical support and the Mito Foundation for a large equipment grant supporting proteomics infrastructure. L.E.F. acknowledges support from the Mito Foundation. A.E.F. and D.R.T. acknowledge additional support from the Mito Foundation and the Victorian Governments Operational Infrastructure Support Program.