The Central Protuberance Region of the Yeast Mitoribosome and its Role in Regulating OXPHOS Complex Biogenesis

线粒体通常被称为细胞的“动力库”，因为它们产生细胞的重要能量货币--三磷酸腺苷。ATP的合成是通过氧化磷酸化(OXPHOS)的过程进行的，该过程由主要由核基因组编码的蛋白质组成的多亚单位酶催化。OXPHOS蛋白的一小部分在线粒体基因组上编码，由线粒体核糖体(有丝分裂糖体)合成，具有重要的酶活性。该项目旨在了解调节有丝分裂糖体活性的分子机制，从而对OXPHOS复合体的组装和细胞的生物能量能力具有重要意义。该项目为本科生和研究生提供机会，旨在促进STEM的发现，同时促进实践学习和培训。还将促进专业发展机会，帮助学生做好职业和/或研究生院的准备，重点是妇女、代表性不足的少数群体和第一代学生。有丝分裂核糖体在进化上与原核糖体有关，已进化到包含新的有丝分裂特异性特征，其功能在很大程度上尚未被探索。本项目的重点是对位于酵母有丝分裂体中央突起(CP)区域的有丝分裂特异蛋白mrpL35/mL38及其伴侣mrp7/bL27的分子解剖。PI最近的发现强调了CP是有丝分裂体的关键调节区，有助于确保翻译过程与OXPHOS复合体组装的下游陪伴事件的协调。该项目的成果将直接适用于从事线粒体生物发生、OXPHOS以及核糖体系统的功能和进化工作的人员。该奖项反映了NSF的法定使命，并已通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Mitochondria are commonly referred to as the 'powerhouse' of the cell because they produce the vital energy currency of the cell, ATP. The synthesis of ATP occurs through a process termed oxidative phosphorylation (OXPHOS), catalyzed by multisubunit enzymes composed mainly of proteins encoded by the nuclear genome. A small, but enzymatically important, subset of OXPHOS proteins are encoded on the mitochondrial genome and synthesized by mitochondrial ribosomes (mitoribosomes). This project seeks to understand the molecular mechanisms that regulate mitoribosome activity, and thus has important implications for the OXPHOS complex assembly and the bioenergetic capacity of the cell. Providing opportunities for both undergraduate and graduate students, this project seeks to advance STEM discovery while promoting hands-on learning and training. Professional development opportunities to aid students with career and/or graduate school preparedness, with a focus on women, underrepresented minorities and first-generation students, will also be promoted.Evolutionarily related to prokaryotic ribosomes, mitoribosomes have evolved to contain novel mitospecific features, the functions of which are largely unexplored. This project is focused on the molecular dissection of the mitospecific protein MrpL35/mL38, and its partner Mrp7/bL27, located in the central protuberance (CP) region of the yeast mitoribosome. The PI's recent findings have highlighted the CP as a key regulatory region of the mitoribosome, serving to ensure coordination of the translational process with the downstream, chaperoned events of OXPHOS complex assembly. The outcomes of this project will be directly applicable to those working on mitochondrial biogenesis, OXPHOS, and the function and evolution of ribosomal systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.