MTABC3, a Novel Mitochondrial ATP-binding Cassette Protein Involved in Iron Homeostasis

• Published in: The Journal of biological chemistry Vol. 275; no. 23; pp. 17536 - 17540
• Main Authors: Mitsuhashi, N, Miki, T, Senbongi, H, Yokoi, N, Yano, H, Miyazaki, M, Nakajima, N, Iwanaga, T, Yokoyama, Y, Shibata, T, Seino, S
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 09.06.2000
• Subjects: Amino Acid Sequence; Animals; ATP-Binding Cassette Transporters - chemistry; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; CHO Cells; chromosome 2; Chromosome Mapping; Chromosomes, Human, Pair 2; Cloning, Molecular; Cricetinae; Exons; Expressed Sequence Tags; Humans; Introns; Iron - metabolism; iron-sulfur clusters; lethal neonatal metabolic syndrome; Mitochondria - metabolism; Molecular Sequence Data; MTABC3 gene; Rats; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Sequence Alignment; Sequence Homology, Amino Acid; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.275.23.17536

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 m i t ochondrial 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.