Disruption of the ATP-binding Cassette B7 (ABTM-1/ABCB7) Induces Oxidative Stress and Premature Cell Death in Caenorhabditis elegans

• DOI: 10.1074/jbc.m110.211201
• Publication Date: 2011-04-05T02:30:17Z
• Authors: Pilar González-Cabo; Arantxa Bolinches...; Juan Cabello; Sheila Ros; Sergio Moreno; Howard A. Baylis; Francesc Palau; Rafael P. Vázquez...
• Keywords: Sideroblastic anemia; Loss function

X-linked sideroblastic anemia with ataxia (XLSA/A) is a rare inherited disorder characterized by mild and ataxia. XLSA/A caused mutations in the ABCB7 gene, which encodes member of ATP-binding cassette transporter family. Studies yeast, mammalian cells, mice have shown that functions transport iron-sulfur (Fe-S) clusters into cytoplasm. To further investigate mechanism this disease, we identified Caenorhabditis elegans homologue abtm-1. We studied function abtm-1 using mutants RNAi. abtm-1-depleted animals produce arrested embryos morphogenetic defects unusual premature, putative apoptotic events. abtm-1(RNAi) also show accumulation ferric iron increased oxidative stress. Despite level stress animals, they an life span. observed DAF-16/FOXO nuclei affected elevation expression SOD-3, well established target DAF-16, may explain span extension these animals. strongly expressed tissues high energy demand, phenotypes reflect need for tissues. Finally, reducing other genes involved Fe-S cluster production produces similar phenotypic consequences to loss function. Therefore, ablation C. provides model underlying XLSA/A.