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，从而保护细胞溶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理解正在增加，但调节过氧化物酶体生物发生或活性的多种有效化学品不可用。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化物酶体调节剂;过氧化物酶体功能，小尺寸和这种生物体的简单遗传学允许直接扰动和增强多细胞生物体中的过氧化物酶体过程。目标1中提出的实验将鉴定和表征降低野生型过氧化物酶体功能的小分子。目的2将鉴定和表征在过氧化物酶体缺陷突变体中改善过氧化物酶体功能的小分子。最后，目标3将确定和表征修饰突变，提高过氧化物酶体功能的过氧化物酶体缺陷突变体。这些目标的成功完成将确定化学物质和分子改变，特别是调节过氧化物酶体生物合成或过氧化物酶体蛋白的进口，提供新的分子工具和理解，阐明和调节过氧化物酶体生物合成和功能，不仅在植物中，而且在其他真核生物。过氧化物酶体缺陷是一组称为过氧化物酶体生物发生障碍的遗传综合征的基础，其通常在婴儿期或儿童期是致命的，并且以包括智力迟钝、神经元迁移缺陷和颅面异常在内的多种症状为特征。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，提供可能适用于整个真核生物的见解。继续开发进化上不同的模型系统来研究过氧化物酶体生物学，将允许假设和机制模型的进步，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.