Peroxisome biogenesis, dynamics, and degradation

项目摘要 过氧化物酶体生物发生、动力学和降解 过氧化物酶体是植物和后生动物生命所必需的真核细胞器。过氧体 隔离各种氧化反应，从而提高代谢效率，同时保护细胞溶质 氧化损伤的成分。尽管我们对过氧化物酶体功能和功能障碍的了解 对这些关键细胞器如何形成、维持和转动的机械理解不断增加 仍然不完整。拟议的研究旨在通过回答以下问题来填补这些空白： 前过氧化物酶体是如何产生的？过氧化物酶体膜复杂性是如何形成的？怎么能 化学探针和遗传抑制剂调节过氧化物酶体功能？如何过时或损坏 过氧化物酶体的目标营业额？过氧化物酶体膜上的泛素化机制 除了受体回收外还兼职吗这些问题将通过拟南芥 thaliana;过氧化物酶体的功能，小尺寸，这种模式植物的简单遗传学允许直接 在完整的多细胞生物体中过氧化物酶体过程的损伤和增强。而且 相对较大的植物过氧化物酶体（与酵母和哺乳动物过氧化物酶体相比）提供了独特的 机会破译过氧化物酶体生物合成和膜错综复杂使用活细胞成像。的 拟议的研究还将培养下一代科学家在最先进的遗传，生物化学， 细胞生物学方法。 过氧化物酶体缺陷是过氧化物酶体生物合成障碍的基础， 通常在婴儿期或儿童期致命的综合征，其特征为多种症状 包括生长不良、多器官功能障碍、听力和视力丧失以及精神发育迟滞。 过氧化物酶体功能障碍也有助于常见的年龄相关疾病（例如，2型神经变性 糖尿病），这些疾病因氧化应激而加剧。拟议的研究将利用植物的独特方面， 过氧化物酶体，同时利用真菌和哺乳动物系统的知识， 很可能适用于整个真核生物。进化上不同的系统的持续发展， 阐明过氧化物酶体生物学的独特优势将推进假说和机制模型， 扩展和完善我们对这一重要细胞器的理解。

PROJECT SUMMARY Peroxisome Biogenesis, Dynamics, and Degradation Peroxisomes are eukaryotic organelles that are essential for life in plants and metazoans. Peroxisomes sequester various oxidative reactions, thereby improving metabolic efficiency while protecting cytosolic constituents from oxidative damage. Although our knowledge about peroxisome function and dysfunction is increasing, mechanistic understanding of how these critical organelles are formed, maintained, and turned over remains incomplete. The proposed studies aim to fill these gaps by answering the following questions: How do pre-peroxisomes originate? How do peroxisomal membrane complexities develop? How can chemical probes and genetic suppressors modulate peroxisome function? How are obsolete or damaged peroxisomes targeted for turnover? Does the ubiquitination machinery on the peroxisomal membrane moonlight in tasks beyond receptor recycling? These questions will be addressed using Arabidopsis thaliana; the peroxisomal functions, small size, and facile genetics of this model plant allow straightforward impairment and enhancement of peroxisomal processes in an intact multicellular organism. Moreover, the relatively large size of plant peroxisomes (compared to yeast and mammalian peroxisomes) offers unique opportunities to decipher peroxisome biogenesis and membrane intricacies using live-cell imaging. The proposed studies also will train the next generation of scientists in state-of-the-art genetic, biochemical, and cell biological approaches. Peroxisomal defects underlie the peroxisome biogenesis disorders, a group of inherited recessive syndromes that are generally fatal in infancy or childhood and are characterized by diverse symptoms including poor growth, multi-organ dysfunctions, hearing and vision loss, and psychomotor retardation. Peroxisome dysfunction also contributes to common age-related diseases (e.g., neurodegeneration, type 2 diabetes) that are exacerbated by oxidative stress. The proposed studies 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. Continued development of evolutionarily distinct systems with unique advantages for elucidating peroxisome biology will advance hypotheses and mechanistic models to expand and refine our understanding of this essential organelle.