title: MTABC3, a novel mitochondrial ATP-binding cassette protein involved in iron homeostasis.
abstract: Atm1p, a mitochondrial half-type ATP-binding cassette (ABC) protein in Saccharomyces cerevisiae, transports a precursor of the iron-sulfur (Fe/S) cluster from mitochondria to the cytosol. We have identified a novel half-type human ABC protein, designating it MTABC3 (mammalian mitochondrial ABC protein 3). MTABC3 mRNA is ubiquitously expressed in all of the rat and human tissues examined. MTABC3 protein is shown to be present in the mitochondria, as assessed by immunoblot analysis and confocal microscopic analysis of subcellular fractions of Chinese hamster ovary cells stably expressing MTABC3. Accumulation of iron in the mitochondria, mitochondrial DNA damage, and respiratory dysfunction in the yeast ATM1 mutant strain (atm1-1 mutant cells) were almost fully reversed by expressing MTABC3 in these mutant cells. These results indicate that MTABC3 is a novel ortholog of the yeast and suggest an important role in mitochondrial function. Interestingly, the human MTABC3 gene has been mapped to chromosome 2q36, a region within the candidate locus for lethal neonatal metabolic syndrome, a disorder of the mitochondrial function associated with iron metabolism, indicating that MTABC3 is a candidate gene for this disorder.
authors.affiliation: Department of Molecular Medicine, Chiba University Graduate School of Medicine, Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Mitsuhashi
authors.forename: T
authors.initials: T
authors.lastname: Miki
authors.forename: H
authors.initials: H
authors.lastname: Senbongi
authors.forename: N
authors.initials: N
authors.lastname: Yokoi
authors.forename: H
authors.initials: H
authors.lastname: Yano
authors.forename: M
authors.initials: M
authors.lastname: Miyazaki
authors.forename: N
authors.initials: N
authors.lastname: Nakajima
authors.forename: T
authors.initials: T
authors.lastname: Iwanaga
authors.forename: Y
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: T
authors.initials: T
authors.lastname: Shibata
authors.forename: S
authors.initials: S
authors.lastname: Seino
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D003001:Cloning, Molecular; D006224:Cricetinae; D005091:Exons; D020224:Expressed Sequence Tags; D006801:Humans; D007438:Introns; D007501:Iron / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection
chemical_list: C107991:ABCB6 protein, human; D018528:ATP-Binding Cassette Transporters; C491540:Abcb6 protein, rat; D011994:Recombinant Proteins; D007501:Iron