heterozygous mutation of opa1 in drosophila shortens lifespan mediated through increased reactive oxygen species production杂合的突变果蝇寿命缩短的opa1介导通过增加活性氧的生产.pdfVIP

Heterozygous Mutation of Opa1 in Drosophila Shortens Lifespan Mediated through Increased Reactive Oxygen Species Production 1 1 1 2,3 1,2,4,5 Sha Tang , Phung Khanh Le , Stephanie Tse , Douglas C. Wallace , Taosheng Huang * 1 Division of Human Genetics, Department of Pediatrics, University of California Irvine, Irvine, California, United States of America, 2 Center for Molecular and Mitochondrial Medicine and Genetics, University of California Irvine, Irvine, California, United States of America, 3 Department of Biological Chemistry, University of California Irvine, Irvine, California, United States of America, 4 Department of Developmental and Cell Biology, University of California Irvine, Irvine, California, United States of America, 5 Department of Pathology, University of California Irvine, Irvine, California, United States of America Abstract Optic atrophy 1 (OPA1) is a dynamin-like GTPase located in the inner mitochondrial membrane and mutations in OPA1 are associated with autosomal dominant optic atrophy (DOA). OPA1 plays important roles in mitochondrial fusion, cristae remodeling and apoptosis. Our previous study showed that dOpa1 mutation caused elevated reactive oxygen species (ROS) production and resulted in damage and death of the cone and pigment cells in Drosophila eyes. Since ROS-induced oxidative damage to the cells is one of the primary causes of aging, in this study, we examined the effects of heterozygous dOpa1 mutation on the lifespan. We found that heterozygous dOpa1 mutation caused shortened lifespan, increased susceptibility to oxidative stress and elevated production of ROS in the whole Drosophila. Antioxidant treatment partially