title: SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy.
abstract: We report mutations in SDHAF1, encoding a new LYR-motif protein, in infantile leukoencephalopathy with defective succinate dehydrogenase (SDH, complex II). Disruption of the yeast homolog or expression of variants corresponding to human mutants caused SDH deficiency and failure of OXPHOS-dependent growth, whereas SDH activity and amount were restored in mutant fibroblasts proportionally with re-expression of the wild-type gene. SDHAF1 is the first bona fide SDH assembly factor reported in any organism.
authors.affiliation: Unit of Molecular Neurogenetics-Pierfranco and Luisa Mariani Center for Study of Children's Mitochondrial Disorders, Foundation IRCCS Neurological Institute C. Besta, Milan, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Ghezzi
authors.forename: Paola
authors.initials: P
authors.lastname: Goffrini
authors.forename: Graziella
authors.initials: G
authors.lastname: Uziel
authors.forename: Rita
authors.initials: R
authors.lastname: Horvath
authors.forename: Thomas
authors.initials: T
authors.lastname: Klopstock
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.forename: Pio
authors.initials: P
authors.lastname: D'Adamo
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
authors.forename: Tim M
authors.initials: TM
authors.lastname: Strom
authors.forename: Holger
authors.initials: H
authors.lastname: Prokisch
authors.forename: Federica
authors.initials: F
authors.lastname: Invernizzi
authors.forename: Ileana
authors.initials: I
authors.lastname: Ferrero
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
mesh_terms: D005816:Genetic Complementation Test; D006801:Humans; D007223:Infant; D007506:Iron-Sulfur Proteins / Q000235:genetics; D056784:Leukoencephalopathies / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D021122:Protein Subunits / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion; D013385:Succinate Dehydrogenase / Q000235:genetics*; D015003:Yeasts / Q000201:enzymology / Q000235:genetics
chemical_list: D007506:Iron-Sulfur Proteins; D021122:Protein Subunits; D011506:Proteins; C553227:SDHAF1 protein, human; D013385:Succinate Dehydrogenase