Presentation description

Mitochondria are a vital organelle due to their role in many metabolic processes and energy production. This central role in cell metabolism causes loss of mitochondrial function to result in many age-associated metabolic disorders. Our lab investigates pathways cells use to preserve mitochondrial homeostasis under response to aging and metabolic and cellular stressors. A main pathway our lab studies is mitochondrial-derived-compartments (MDCs), a mitochondrial remodeling pathway removing excess or damaged proteins from the outer mitochondrial membrane (OMM). Currently, it's unknown how MDCs form from the OMM or target cargo proteins into MDCs for degradation. We hypothesize the OMM protein, Tom70, a protein involved in mitochondrial protein import, is important for MDC formation since tom70∆ cells have less MDCs. In this project, to examine how Tom70 supports MDC formation we utilized budding yeast, Saccharomyces cerevisiae, and CRISPR/Cas9 to mutate domains of Tom70. By studying a model of Tom70, we made amino acid substitutions with alanine in areas with high sequence conservation within the chaperone binding domain, precursor protein binding domain, and dimerization interface of Tom70. Subsequently, we analyzed the effect of these mutations on supporting MDC formation and cell proliferation at high temperatures. Thus far, our results indicate the chaperone binding domain of Tom70 isn't required for MDC formation, which was surprising as this function of Tom70 is important for chaperoning proteins during heat-induced protein stress. In future studies, we hope to learn which domains of Tom70 are important for MDC formation, but don't affect other functions of the protein.