The effects of exogenous ubiquinone on mitochondrial function, oxidative damage, and lifespan in Caenorhabditis elegans

The interactions between mitochondrial function, reactive oxygen species (ROS), and lifespan are incompletely understood. Using the nematode C. elegans, this thesis attempts to clarify these interactions. The study focuses on the long-lived mutant clk-1 which is defective in synthesis of the electron carrier, ubiquinone. The work further investigates the role of ubiquinone on the following: 1) Mitochondrial respiration. 2) The site and rate of ROS production. 3) ROS scavenging. 4) The oxidation of mitochondrial proteins.;Besides the studies of effects from different exogenous UQ, I also characterized the possible effects of the ubiquinone biosynthetic precursor, demethoxyubiquinone-9 (DMQ9) on mitochondrial electron transport and on phenotypes of clk-1 .;My thesis project integrates the comprehensive biochemical approach and C. elegans genetics to elucidate the mitochondrial effects on the variation in longevity. The results indicate that UQ10 extends the lifespan of clk-1 by lowering oxidative damage in mitochondrial proteins, but does not decrease ROS production. Moreover, DMQ9 inhibits electron transport from Complex I to III, which results in the defective Complex I-dependent respiration in clk-1. These results link the physiological changes within mitochondria caused by exogenous ubiquinone to aging and longevity.