A novel Drosophila SOD2 mutant demonstrates a role for mitochondrial ROS in neurodevelopment and disease

Brain and Behavior

Alicia M. Celotto¹  Zhaohui Liu¹  Andrew P. VanDemark² 

[1] Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania

关键词: Drosophila melanogaster;    MnSOD;    motoneuron axonal targeting;    roGFP;    ROS;    SOD2;   

DOI  :  10.1002/brb3.73

来源: Wiley

【 摘 要 】

Abstract

Reactive oxygen species (ROS) play essential roles in cell signaling, survival, and homeostasis. Aberrant ROS lead to disease and contribute to the aging process. Numerous enzymes and vigilant antioxidant pathways are required to regulate ROS for normal cellular health. Mitochondria are a major source of ROS, and mechanisms to prevent elevated ROS during oxidative phosphorylation require super oxide dismutase (SOD) activity. SOD2, also known as MnSOD, is targeted to mitochondria and is instrumental in regulating ROS by conversion of superoxides to hydrogen peroxide, which is further broken down into H₂O and oxygen. Here, we describe the identification of a novel mutation within the mitochondrial SOD2 enzyme in Drosophila that results in adults with an extremely shortened life span, sensitivity to hyperoxia, and neuropathology. Additional studies demonstrate that this novel mutant, SOD2^bewildered, exhibits abnormal brain morphology, suggesting a critical role for this protein in neurodevelopment. We investigated the basis of this neurodevelopmental defect and discovered an increase in aberrant axonal that could underlie the aberrant neurodevelopment and brain morphology defects. This novel allele, SOD2^bewildered, provides a unique opportunity to study the effects of increased mitochondrial ROS on neural development, axonal targeting, and neural cell degeneration in vivo.

【 授权许可】

CC BY-NC   
© 2012 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.