SGER: The Role of Lipid Bodies in Peroxisomal Biogenesis

SGER：脂质体在过氧化物酶体生物发生中的作用

• 批准号: 0455329
• 负责人: Joel Goodman
• 金额: --
• 依托单位: University of Texas Southwestern Medical Center
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-15 至 2007-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0455329&HistoricalAwards=false
• 关键词: SGER; Role; Lipid; Bodies; Peroxisomal

Peroxisomes are found in virtually all eukaryotic cells. They are essential organelles for many metabolic pathways in plants, fungi, and animals. The origin of peroxisomes has been hotly debated for decades. It is clear now that peroxisomes can form by fission from pre-existing peroxisomes. However, there is ample evidence for a de novo pathway of peroxisomal assembly. The endoplasmic reticulum (ER) has been implicated in this pathway, although its precise role has not been established. There have also been reports of close associations between lipid bodies (which form from the ER) and peroxisomes, although the significance of these observations is not known. This project will test the hypothesis that lipid bodies are essential for the de novo assembly of peroxisomes in yeast. As a first step, the extent to which peroxisomal proteins reside in the lipid body-associated structures will be determined. The direct test for the hypothesis will be accomplished by looking for a precursor-product relationship between these structures and mature peroxisomes. Further confirmation will be accomplished by examining the extent of peroxisomal biogenesis in a mutant that cannot generate lipid bodies nor undergo fission of preexisting organelles. This project thus tests a completely new model for the origin of peroxisomes. The de novo origin of peroxisomes has been a murky and controversial subject to date, and our hypothesis is consistent with several observations in the literature and could solve this controversy. If the hypothesis is correct, it would overturn current thinking of organelle biogenesis, indicating that the lipid body is capable of this activity. The project will also provide hands-on research experience for high school (underprivileged), undergraduate, and graduate students. Results will be widely disseminated through talks at national meetings and submission to first-tier science journals.

过氧化物酶体几乎存在于所有真核细胞中。它们是植物、真菌和动物许多代谢途径必不可少的细胞器。关于过氧化物酶体的起源已经争论了几十年。现在很清楚，过氧化物酶体可以由已有的过氧化物酶体通过裂变形成。然而，有充分的证据表明，过氧化物酶体组装的新途径。内质网（ER）参与了这一途径，尽管其确切作用尚未确定。也有报道称脂质体（由内质网形成）和过氧化物酶体之间存在密切联系，尽管这些观察结果的意义尚不清楚。该项目将验证脂质体对酵母中过氧化物酶体的重新组装至关重要的假设。作为第一步，将确定过氧化物酶体蛋白驻留在脂质体相关结构中的程度。该假设的直接检验将通过寻找这些结构和成熟过氧化物酶体之间的前体-产物关系来完成。进一步的确认将通过检查突变体中过氧化物酶体的生物发生程度来完成，该突变体不能产生脂质体，也不能经历先前存在的细胞器的裂变。因此，这个项目测试了一个关于过氧化物酶体起源的全新模型。迄今为止，过氧化物酶体的从头起源一直是一个模糊和有争议的主题，我们的假设与文献中的几个观察结果一致，可以解决这一争议。如果这个假设是正确的，它将推翻目前关于细胞器生物发生的想法，表明脂质体能够进行这种活动。该项目还将为高中（弱势群体）、本科生和研究生提供实践研究经验。研究结果将通过在国家会议上的演讲和向一流科学期刊投稿的方式广泛传播。