Antioxidant metabolism in Chlamydomonas

描述（由申请人提供）：几种由植物合成的抗氧化剂小分子是人类饮食中必需的维生素。这些营养物质，包括维生素A前体（类胡萝卜素）、维生素E（生育酚）和维生素C（抗坏血酸），在猝灭和清除活性氧方面具有关键作用，活性氧是所有需氧生物（从细菌到植物和动物）新陈代谢不可避免的副产物。尽管抗氧化维生素对人体健康很重要，但关于它们的功能及其生物合成的调控，许多基本问题仍未得到解答。本研究利用分子遗传学、基因组学和生理学方法对一种单细胞绿藻莱茵衣藻进行了研究。衣藻是研究植物抗氧化代谢的一种强大的真核模式生物，就像酿酒酵母被用作动物的模型一样。本课题的具体目的是：(1)完成衣藻类胡萝卜素生物合成的分子和遗传分析；(2)生成一系列影响生育酚组成的突变体，以测试体内不同生育酚的抗氧化功能；(3)研究类胡萝卜素和生育酚在多不饱和脂膜中作为抗氧化剂的功能重叠。(4)对细胞内的类胡萝卜素和生育酚水平如何受环境因素（如光照强度）调节进行基因组和遗传分析。该研究将为脂溶性抗氧化剂在预防黄斑变性等衰老相关疾病中的作用提供新的认识，并为合理修改植物中类胡萝卜素和生育酚的组成和含量提供基础，从而有益于人类的营养和健康。

DESCRIPTION (provided by applicant): Several antioxidant small molecules that are synthesized by plants are essential vitamins in the human diet. These nutrients, including vitamin A precursors (carotenoids), vitamin E (tocopherols), and vitamin C (ascorbate), have critical functions in quenching and scavenging reactive oxygen species that are inevitable byproducts of metabolism in all aerobic organisms, from bacteria to plants and animals. Despite the importance of antioxidant vitamins for human health, many fundamental questions remain unanswered about their function and the regulation of their biosynthesis. This proposal addresses several of these questions using molecular genetic, genomic, and physiological approaches in a tractable, unicellular green alga, Chlamydomonas reinhardti. Chlamydomonas represents a powerful eukaryotic model organism for studying antioxidant metabolism in plants, much like the budding yeast Saccharomyces cerevisiae is used as a model for animals. The specific aims of this proposal are (1) to complete a molecular and genetic analysis of carotenoid biosynthesis in Chlamydomonas, (2) to generate a series of mutants affecting tocopherol composition in order to test the antioxidant function of different tocopherols in vivo, (3) to examine functional overlap between carotenoids and tocopherols as antioxidants in polyunsaturated lipid membranes, and (4) to perform genomic and genetic analyses of how carotenoid and tocopherol levels are regulated in cells by environmental factors, such as light intensity. This investigation will provide new insights into the roles of lipid-soluble antioxidants in preventing age-related diseases such as macular degeneration in humans and will provide a foundation for rational modification of carotenoid and tocopherol composition and content in plants to benefit human nutrition and health.