Chemical and genetic modifiers of peroxisome function in Arabidopsis

描述（由申请人提供）：过氧化物酶体是真核细胞器，可隔离各种氧化反应，从而保护胞质成分免受氧化损伤。虽然对过氧化物酶体功能和功能障碍的生物学后果的了解正在增加，但调节过氧化物酶体生物发生或活性的多种有效化学物质尚不存在。拟议的研究将鉴定和表征模式植物拟南芥中的化学和遗传过氧化物酶体调节剂；这种生物体的过氧化物酶体功能，小尺寸和易遗传，允许在多细胞生物体中直接扰动和增强过氧化物酶体过程。Aim 1中提出的实验将鉴定和表征野生型中降低过氧化物酶体功能的小分子。目的2将鉴定和表征改善过氧化物酶体缺陷突变体中过氧化物酶体功能的小分子。最后，Aim 3将鉴定和表征改善过氧化物酶体缺陷突变体中过氧化物酶体功能的修饰突变。这些目标的成功完成将确定特异性调节过氧化物酶体生物发生或过氧化物酶体蛋白质输入的化学物质和分子改变，为阐明和调节植物以及其他真核生物中的过氧化物酶体生物发生和功能提供新的分子工具和理解。过氧化物酶体缺陷是一组被称为过氧化物酶体生物发生障碍的遗传综合征的基础，通常在婴儿期或儿童期是致命的，其特征是多种症状，包括智力迟钝、神经元迁移缺陷和颅面异常。拟议的实验将利用植物过氧化物酶体的独特方面，同时利用真菌和哺乳动物系统的知识来提供可能适用于整个真核生物的见解。继续发展进化上独特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基本细胞器的理解。

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.