title: CIA30 complex I assembly factor: a candidate for human complex I deficiency?
abstract: The human mitochondrial NADH:ubiquinone oxidoreductase (complex I), the first complex of the oxidative phosphorylation system, is composed of at least 42 subunits. Little is known about the assembly process of these subunits into the mature complex. Recently, two proteins in Neurospora crassa have been found to be involved in the assembly of complex I. These proteins are not constituent parts of the mature complex but are associated with smaller intermediate complexes of the assembly process and have a chaperone-like function. We have characterized the human homologue of one of these two complex I intermediate associated proteins, named CIA30, and show that expression of the human CIA30 protein is ubiquitous with a slightly higher expression in various heart tissues, kidney, lung and liver. As deletion of the Neurospora crassa CIA genes results in severe disruption of the assembly process, human CIA30 can be considered as a candidate gene related to complex I deficiency. Thirteen patients with an isolated complex I deficiency, but who were ruled out for mutations in the 35 nuclear genes of the complex and mtDNA, were subjected to mutational analysis of the gene coding for the human CIA30 protein. Four new single nucleotide polymorphisms (SNPs) were detected but no functional mutation was found.
authors.affiliation: Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Rolf
authors.initials: R
authors.lastname: Janssen
authors.forename: Jan
authors.initials: J
authors.lastname: Smeitink
authors.forename: Roel
authors.initials: R
authors.lastname: Smeets
authors.forename: Lambert
authors.initials: L
authors.lastname: van Den Heuvel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D042967:Electron Transport Complex I; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D021122:Protein Subunits; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014018:Tissue Distribution
chemical_list: D004272:DNA, Mitochondrial; D021122:Protein Subunits; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I