Open AccessSideroflexin 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) -
Thomas Daniel Jackson,
Jordan J. Crameri,
Linden Muellner-Wong,
Ann E Frazier,
Catherine S Palmer,
Luke E. Formosa,
Daniella H Hock,
Kenji M. Fujihara,
Tegan Stait,
Alice J. Sharpe,
David R. Thorburn,
Michael Ryan,
David A. Stroud,
Diana Stojanovski
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2115566119
Subject(s) - mitochondrion , organelle , microbiology and biotechnology , function (biology) , mutation , biology , mitochondrial fusion , chemistry , gene , genetics , mitochondrial dna
Significance Mitochondria 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 inSFXN4 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.