Caenorhabditis elegans -- Genetics, Mitochondria, Cancer -- Genetic aspects, Genomic Instability
Many terminal human diseases are caused by mutations affecting mitochondrial functioning. Mitochondria are essential organelles responsible for producing cellular energy, adenosine triphosphate (ATP) via oxidative phosphorylation (OXPHOS) at mitochondrial electron transport chains (ETC). Proper ETC functioning relies on maintenance of the electrochemical gradient essential for energy production, known as mitochondrial membrane potential (ΔψM). The inner mitochondrial membrane is the site of the ETC and is most closely in contact with the enzymatic processes occurring within the mitochondrial matrix. Mutations affecting protein components of the ETC are especially troublesome for organelle health. ETC mutants commonly express altered ΔψM, as well as increased production of damaging reactive oxygen species (ROS), which are hypothesized to cause genomic damage and lasting mutation. The nematode C. elegans is a practical model organism for investigating the phenotypic and genomic consequences of ETC mutations. Despite expressing higher levels of damaging ROS, the ETC protein complex 1 mutant, gas-1, expresses heritable mtDNA and nDNA mutation rates identical to those of wild type animals. I am using a mitochondria-targeted dye and fluorescence microscopy to quantify and compare ΔψM levels of the gas-1 mutant and wild type animals. This work will provide a novel phenotypic characterization of this mutant and indicate whether decreased metabolic activity (e.g., reduced reliance on OXPHOS) is occurring in gas-1, and perhaps conferring protection from genomic degradation. Based on gas-1’s characteristically low ATP production and high ROS production, I expect that ΔψM will be higher in gas-1 as compared to wild type levels.
Muñoz-Tremblay, Lauren S.
"Role of Metabolic Shifts in Protection from Mutation Damage: Characterizing Mitochondrial Membrane Potential in C. Elegans Gas-1 Mutants,"
PSU McNair Scholars Online Journal:
1, Article 7.