Peroxisome biogenesis, dynamics, and degradation

过氧化物酶体生物发生、动力学和降解

• 批准号: 10725078
• 负责人: Bonnie Bartel
• 金额: $ 7.06万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2024-01-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10725078
• 关键词: Address; Biochemical; Biogenesis; Biological; Biology; Blindness; Cells; Chemicals; Childhood; Defect; Development; Disease; Eukaryota; Functional disorder; Genetic; Genetic Models; Growth; Human Development; Impairment; Inherited; Knowledge; Life; Membrane; Metabolic; Modeling; Molecular; Mouse-ear Cress; Nerve Degeneration; Non-Insulin-Dependent Diabetes Mellitus; Organ; Organelles; Organism; Oxidative Stress; Plant Model; Plants; Process; Reaction; Regulation; Scientist; Symptoms; Syndrome; System; Training; Ubiquitination; Yeasts; age related; experimental study; hearing impairment; improved; infancy; insight; live cell imaging; next generation; oxidative damage; peroxisome; plant growth/development; receptor recycling

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.

项目总结 过氧化物体的生物发生、动力学和降解 过氧化物体是真核生物的细胞器，对植物和后生动物的生命是必不可少的。过氧酶体 隔离各种氧化反应，从而提高代谢效率，同时保护胞浆 氧化损伤的成分。尽管我们对过氧化物酶的功能和功能障碍的了解是 增加对这些关键细胞器如何形成、维持和转动的机械性理解 Over仍未完成。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起源的？过氧化物酶体膜复合体是如何发展起来的？怎么能 化学探针和基因抑制物调节过氧化物酶的功能？如何过时或损坏 目标是周转的过氧酶体？过氧化体膜上的泛素化机制 在受体回收之外的任务中的月光？这些问题将用拟南芥来解决 这种模式植物的过氧体功能、小体积和简单的遗传学使得 完整的多细胞生物体中过氧化体突起的损伤和增强。此外， 相对较大的植物过氧化物体(与酵母和哺乳动物的过氧化物体相比)提供了独特的 使用活细胞成像破译过氧化体生物发生和膜的错综复杂的机会。这个 拟议中的研究还将培训下一代科学家在最先进的遗传学、生化和 细胞生物学方法。 过氧化物酶体缺陷是一组遗传性隐性遗传性生物发生障碍的基础 在婴儿期或儿童期通常是致命的，以各种症状为特征的综合征 包括发育不良、多器官功能障碍、听力和视力丧失以及精神运动发育迟缓。 过氧化物酶体功能障碍也会导致常见的与年龄相关的疾病(如神经变性、2型 糖尿病)，氧化应激会加剧这些疾病。拟议的研究将利用植物的独特方面。 利用真菌和哺乳动物系统的知识提供洞察力 很可能适用于整个真核生物。进化上截然不同的系统的持续发展 阐明过氧酶体生物学的独特优势将推动假说和机制模型 扩展和提炼我们对这一重要细胞器的理解。