SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy.
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.
Ghezzi
Daniele
D
Unit of Molecular Neurogenetics-Pierfranco and Luisa Mariani Center for Study of Children's Mitochondrial Disorders, Foundation IRCCS Neurological Institute C. Besta, Milan, Italy.
Goffrini
Paola
P
Uziel
Graziella
G
Horvath
Rita
R
Klopstock
Thomas
T
Lochmüller
Hanns
H
D'Adamo
Pio
P
Gasparini
Paolo
P
Strom
Tim M
TM
Prokisch
Holger
H
Invernizzi
Federica
F
Ferrero
Ileana
I
Zeviani
Massimo
M
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
D007506:Iron-Sulfur Proteins; D021122:Protein Subunits; D011506:Proteins; C553227:SDHAF1 protein, human; D013385:Succinate Dehydrogenase