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

Marquette University, Milwaukee WI

Investigators

Abstract

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.