title: A Single Adaptable Cochaperone-Scaffold Complex Delivers Nascent Iron-Sulfur Clusters to Mammalian Respiratory Chain Complexes I-III.
abstract: The iron-sulfur (Fe-S) cluster of the Rieske protein, UQCRFS1, is essential for Complex III (CIII) activity, though the mechanism for Fe-S cluster transfer has not previously been elucidated. Recent studies have shown that the co-chaperone HSC20, essential for Fe-S cluster biogenesis of SDHB, directly binds LYRM7, formerly described as a chaperone that stabilizes UQCRFS1 prior to its insertion into CIII. Here we report that a transient subcomplex involved in CIII assembly, composed of LYRM7 bound to UQCRFS1, interacts with components of an Fe-S transfer complex, consisting of HSC20, its cognate chaperone HSPA9, and the holo-scaffold ISCU. Binding of HSC20 to the LYR motif of LYRM7 in a pre-assembled UQCRFS1-LYRM7 intermediate in the mitochondrial matrix facilitates Fe-S cluster transfer to UQCRFS1. The five Fe-S cluster subunits of Complex I also interact with HSC20 to acquire their clusters, highlighting the crucial role of HSC20 in the assembly of the mitochondrial respiratory chain.
authors.affiliation: Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Nunziata
authors.initials: N
authors.lastname: Maio
authors.affiliation: Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Ki Soon
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Anamika
authors.initials: A
authors.lastname: Singh
authors.affiliation: Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 9000 Rockville Pike, Bethesda, MD 20892, USA. Electronic address: rouault@mail.nih.gov.
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Rouault
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D004579:Electron Transport; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D055786:Gene Knockout Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D008322:Mammals / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D045222:Electron Transport Chain Complex Proteins; C490651:HSCB protein, human; D007506:Iron-Sulfur Proteins; C000588844:LYRM7 protein, human; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; C579514:UQCRFS1 protein, human
keywords: Complex I; Complex II; Complex III; HSC20; HSPA9; ISCU; LYRM7; iron sulfur biogenesis; mitochondrial respiratory chain