Sideroflexin 4 is a complex I assembly factor that interacts with the MCIA complex and is required for the assembly of the ND2 module
- Author(s)
- Jackson, TD; Crameri, JJ; Muellner-Wong, L; Frazier, AE; Palmer, CS; Formosa, LE; Hock, DH; Fujihara, KM; Stait, T; Sharpe, AJ; Thorburn, DR; Ryan, MT; Stroud, DA; Stojanovski, D;
- Details
- Publication Year 2022-03-29,Volume 119,Issue #13,Page e2115566119
- Journal Title
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type
- Research article
- Abstract
- SignificanceMitochondria are double-membraned eukaryotic organelles that house the proteins required for generation of ATP, the energy currency of cells. ATP generation within mitochondria is performed by five multisubunit complexes (complexes I to V), the assembly of which is an intricate process. Mutations in subunits of these complexes, or the suite of proteins that help them assemble, lead to a severe multisystem condition called mitochondrial disease. We show that SFXN4, a protein that causes mitochondrial disease when mutated, assists with the assembly of complex I. This finding explains why mutations in SFXN4 cause mitochondrial disease and is surprising because SFXN4 belongs to a family of amino acid transporter proteins, suggesting that it has undergone a dramatic shift in function through evolution.
- Keywords
- Adenosine Triphosphate/metabolism; *Electron Transport Complex I/metabolism; Humans; Membrane Proteins; Mitochondria/genetics/metabolism; *Mitochondrial Diseases/genetics; Mitochondrial Proteins/genetics/metabolism; Mutation; complex assembly; mitochondria; respiratory chain; sideroflexins
- Department(s)
- Laboratory Research
- PubMed ID
- 35333655
- Publisher's Version
- https://doi.org/10.1073/pnas.2115566119
- Open Access at Publisher's Site
https://doi.org/10.1073/pnas.2115566119- Terms of Use/Rights Notice
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Creation Date: 2024-12-18 06:40:29
Last Modified: 2024-12-18 06:41:56