A novel Drosophila SOD2 mutant demonstrates a role for mitochondrial ROS in neurodevelopment and disease.
A novel Drosophila SOD2 mutant demonstrates a role for mitochondrial ROS in neurodevelopment and disease.
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DOI：
10.1002/brb3.73
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发表时间：
2012-07
影响因子：
3.1
通讯作者：
Palladino, Michael J.
中科院分区：
文献类型：
--
作者：
Celotto, Alicia M.;Liu, Zhaohui;VanDemark, Andrew P.;Palladino, Michael J.
活性氧(ROS)在细胞信号转导、生存和动态平衡中起着至关重要的作用。ROS异常会导致疾病，并促进衰老过程。许多酶和警觉的抗氧化途径是调节ROS以维持正常细胞健康所必需的。线粒体是ROS的主要来源，而在氧化磷酸化过程中防止ROS升高的机制需要超氧化物歧化酶(SOD)的活性。Sod2，也被称为MnSOD，针对线粒体，通过将超氧化物转化为过氧化氢来调节ROS，过氧化氢进一步分解为H2O和氧气。在这里，我们描述了在果蝇中鉴定出线粒体SOD2酶内的一种新的突变，该突变导致成年果蝇寿命极短，对高氧敏感，以及神经病理。更多的研究表明，这一新的突变体SOD2困惑，显示出异常的大脑形态，表明该蛋白在神经发育中起着关键作用。我们调查了这种神经发育缺陷的基础，发现异常轴突的增加可能是神经发育异常和脑形态缺陷的基础。这种新的等位基因，SOD2，提供了一个独特的机会来研究体内线粒体ROS增加对神经发育、轴突靶向和神经细胞退化的影响。
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, SOD2bewildered, 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, SOD2bewildered, provides a unique opportunity to study the effects of increased mitochondrial ROS on neural development, axonal targeting, and neural cell degeneration in vivo.
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影响因子：
3.1
作者：
Belton, Amy;Paul, Anirban;Duttaroy, Atanu
通讯作者：
Duttaroy, Atanu
DOI：
10.1073/pnas.252342899
发表时间：
2002-12-10
影响因子：
11.1
作者：
Kirby, K;Hu, JG;Phillips, JP
通讯作者：
Phillips, JP
影响因子：
3.3
作者：
Fergestad, Tim;Bostwick, Bret;Ganetzky, Barry
通讯作者：
Ganetzky, Barry
影响因子：
2.9
作者：
Cabelli, DE;Guan, Y;Silverman, DN
通讯作者：
Silverman, DN
影响因子：
2.9
作者：
Greenleaf, WB;Jefferson, J;Silverman, DN
通讯作者：
Silverman, DN