title: LYRM7/MZM1L is a UQCRFS1 chaperone involved in the last steps of mitochondrial Complex III assembly in human cells.
abstract: The mammalian Complex III (CIII) assembly process is yet to be completely understood. There is still a lack in understanding of how the structural subunits are put together and which additional factors are involved. Here we describe the identification and characterization of LYRM7, a human protein displaying high sequence homology to the Saccharomyces cerevisiae protein Mzm1, which was recently shown as an assembly factor for Rieske Fe-S protein incorporation into the yeast cytochrome bc(1) complex. We conclude that human LYRM7, which we propose to be renamed MZM1L (MZM1-like), works as a human Rieske Fe-S protein (UQCRFS1) chaperone, binding to this subunit within the mitochondrial matrix and stabilizing it prior to its translocation and insertion into the late CIII dimeric intermediate within the mitochondrial inner membrane. Thus, LYRM7/MZM1L is a novel human CIII assembly factor involved in the UQCRFS1 insertion step, which enables formation of the mature and functional CIII enzyme.
authors.affiliation: Unidad de Investigación Traslacional, Hospital Universitario Miguel Servet, Zaragoza, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Sánchez
authors.forename: Teresa
authors.initials: T
authors.lastname: Lobo
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Fox
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Winge
authors.forename: Erika
authors.initials: E
authors.lastname: Fernández-Vizarra
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D014450:Electron Transport Complex III / Q000378:metabolism* / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D051379:Mice; D024101:Mitochondrial Proteins / Q000378:metabolism* / Q000502:physiology; D018832:Molecular Chaperones / Q000378:metabolism* / Q000502:physiology; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C435491:BCS1L protein, human; D007506:Iron-Sulfur Proteins; C538836:LYRM1 protein, human; C000588844:LYRM7 protein, human; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; C579514:UQCRFS1 protein, human; C568504:mitochondrial zinc maintenance protein 1, S cerevisiae; D000074183:ATPases Associated with Diverse Cellular Activities; D014450:Electron Transport Complex III