Role of SUV3 in Maintaining Yeast Mitochondrial Homeostasis

Yeast SUV3 is a nuclear encoded mitochondrial RNA helicase that complexes with exoribonuclease, DSS1, to function as a RNA degradosome. Inactivation of SUV3 leads to mitochondrial dysfunctions such as respiratory deficiency, accumulation of aberrant RNA species including excised group I introns, and loss of mitochondrial DNA (mtDNA). Although intron toxicity has long been speculated as the major reason for the observed phenotypes, a direct evidence to support this theory is lacking. Furthermore, how SUV3 coordinates the proper intron turnover with the maintenance of mitochondrial genome remains elusive.;Herein this dissertation, I document my experimental work in contribution to the understanding of the role of SUV3 in maintaining yeast mitochondrial homeostasis. Using inducible systems and yeast genetics analyses, I first dissected the structural and functional relationship of C-terminal domain of SUV3. My investigations demonstrated a DSS1 binding motif and conserved region (CC) that are essential for SUV3 functions. Then, I scrutinized the different behaviors of SUV3 with either normal or intronless mtDNA background, providing the first direct evidence supporting the notion that the functional requirements of SUV3 for degradosome activity and maintenance of mitochondrial genome stability are separable. Lastly, I explored the potential role of SUV3 in maintaining mitochondrial genome stability. My results showed that loss of SUV3 is associated with loss of active replicating mitochondrial nucleoids and the intact ATPase activity and the CC conserved region are indispensible.;Thus, based on my experimental research, I purport here that SUV3 is vital for mitochondrial homeostasis by maintaining both intron turnover and mtDNA replication.