Hui Zhong
Role of Zn2+ and Zn2+-Binding Proteins in the Assembly and Structural Integrity of Mitochondrial Ribosomes
Poster Presenter #55
Ph.D. in Biochemical and Molecular Biology
The ribosome is the essential macromolecule for protein synthesis in all kingdoms of life. In eukaryotic cells, mitochondria harbor a distinct class of ribosomes (mitoribosomes) of bacterial origin. Mitoribosomes are specialized on the synthesis of a small set of hydrophobic proteins (13 in human cells) encoded in the mitochondrial DNA, a remnant of the proteobacterial ancestor genome. These proteins are all components of the oxidative phosphorylation (OXPHOS) system, responsible for the aerobic conversion of energy stored in nutrients into adenosine triphosphate (ATP). Therefore, mitoribosome biogenesis and function are essential for aerobic energy metabolism and thus is not surprising that defective mitochondrial protein synthesis has been associated to mitochondrial cardio- and encephalo-myopathies, hearing loss and cancer. Currently, high-resolution structures of the mammalian and yeast mitoribosome have been disclosed by cryo-EM. The assembly pathways of yeast and human mitoribosomes are also starting to emerge. However, many questions remain regarding the regulation of mitoribosome biogenesis and function, whose full understanding is the long-term goal of our laboratory. In this project, we will follow the observation in cryo-EM structures that the human mitoribosome contains ten Zn2+-binding proteins. Divalent metal ions such as Zn2+ are essential for live. Zn2+-binding proteins are widely present across cells and are known to facilitate a variety of processes. Zn2+-binding motifs serve as critical mediators in protein structure, catalysis and regulation. Intracellular Zn2+ homeostasis is strictly regulated by Zn2+ binding proteins and Zn2+ transporters. Yet, the role of Zn2+ and Zn2+-binding proteins in the structural stability and function of human mitoribosomes remains unexplored. The main objectives of this project are to understand the roles of Zn2+ and Zn2+-binding proteins in human mitoribosome assembly, stability, subunit association and protein synthesis. We hypothesize that Zn2+ and Zn2+-binding proteins are essential for normal tertiary and quaternary structures of mitoribosome proteins (MRPs) and subunits. This project is relevant from biological and biomedical perspectives. The knowledge identified above is expected to impact the broad fields of mitochondrial biology, ribosome biogenesis and transition metal homeostasis. Our studies may therefore reveal actual and potential pathogenic mechanisms involving Zn2+-binding mitoribosome proteins.