Chemical and genetic modifiers of peroxisome function in Arabidopsis

描述(申请人提供)：过氧体是真核细胞器，它隔离各种氧化反应，从而保护细胞质成分免受氧化损伤。尽管人们对过氧酶体功能和功能障碍的生物学后果的了解越来越多，但调节过氧酶体生物发生或活性的各种有效化学物质尚不存在。拟议的研究将确定和表征模式植物拟南芥中的化学和遗传过氧体调节剂；这种生物的过氧体功能、小体积和简单的遗传学允许直接干扰和增强多细胞生物体中的过氧体过程。在目标1中提出的实验将识别和表征在野生型中降低过氧化物体功能的小分子。目的2将鉴定和表征小分子改善过氧化物体功能的过氧化物体缺陷突变体。最后，目标3将识别和表征修饰突变，这些突变可以改善过氧化物体缺陷突变体中的过氧化物体功能。这些目标的成功完成将识别特异性调节过氧化物体生物发生或过氧体蛋白输入的化学物质和分子变化，为阐明和调节过氧化物体的生物发生和功能提供新的分子工具和理解，不仅在植物中，而且在其他真核生物中也是如此。过氧化体缺陷是一组被称为过氧化体生物发生障碍的遗传综合征的基础，这些综合征通常在婴儿期或儿童期是致命的，其特征是各种症状，包括智力低下、神经元迁移缺陷和颅面畸形。拟议的实验将利用植物过氧化物体的独特方面，同时利用真菌和哺乳动物系统的知识来提供可能适用于真核生物的见解。继续开发进化上截然不同的模型系统来研究过氧化物酶体生物学，将允许假说和机制模型的进步，以扩大和完善我们对这些重要细胞器的理解。

DESCRIPTION (provided by applicant): Peroxisomes are eukaryotic organelles that sequester various oxidative reactions, thereby protecting cytosolic constituents from oxidative damage. Although understanding of the biological consequences of peroxisome function and dysfunction is increasing, diverse and effective chemicals that modulate peroxisome biogenesis or activity are not available. The proposed studies will identify and characterize chemical and genetic peroxisome modulators in the model plant Arabidopsis thaliana; the peroxisomal functions, small size, and facile genetics of this organism allow straightforward perturbation and enhancement of peroxisomal processes in a multicellular organism. The experiments proposed in Aim 1 will identify and characterize small molecules that reduce peroxisome function in wild type. Aim 2 will identify and characterize small molecules that improve peroxisome function in peroxisome-defective mutants. Finally, Aim 3 will identify and characterize modifier mutations that improve peroxisome function in peroxisome-defective mutants. The successful completion of these aims will identify chemicals and molecular alterations that specifically modulate peroxisome biogenesis or peroxisomal protein import, providing new molecular tools and understanding with which to elucidate and modulate peroxisome biogenesis and function not only in plants, but also in other eukaryotes. Peroxisomal defects underlie a group of inherited syndromes known as peroxisome biogenesis disorders, which are generally fatal in infancy or childhood and are characterized by diverse symptoms including mental retardation, neuronal migration defects, and craniofacial abnormalities. The proposed experiments will exploit unique aspects of plant peroxisomes while taking advantage of knowledge from fungal and mammalian systems to provide insights that are likely to apply throughout eukaryotes. Continuing to develop evolutionarily distinct model systems with which to study peroxisome biology will allow advancement of hypotheses and mechanistic models to expand and refine our understanding of these essential organelles.