Graham Walker’s HHMI Education Group has allowed him to develop new tools and curricula for undergraduate biology while training young research scientists to become educators. The group’s members participate in a variety of teaching and educational projects, and play leadership roles in the continuing development, dissemination, and assessment of the student-friendly biology digital learning tools StarBiochem, StarGenetics, and StarCellBio.
Determining the Role of the Lon Protease in Mitochondrial DNA Maintenance
All cells encounter stresses that threaten their ability not only to survive but also to function properly. Our lab studies how cells cope with stresses that damage their DNA. We have recently become interested in how the mitochondria of eukaryotic cells respond when cells are exposed to DNA-damaging agents. Mitochondria contain their own genome (mitochondrial DNA [mtDNA]) and are involved in energy production, programmed cell death, calcium buffering, production of free radicals known as reactive oxygen species, and production of cofactors called iron sulfur clusters. We have found that a protein known as the Lon protease is produced at a much higher level in the mitochondria of cells that have been exposed to a DNA damaging-agent and chemotherapeutic cisplatin. The Lon protease, which serves many functions in mitochondrial quality control, rids the cells of harmful damaged proteins, yet it is also important in maintaining the integrity of the mitochondrial genome. We have developed an experimental system in the yeast Saccharomyces cerevisiae where we can track the integrity of mtDNA while we control the amount of Lon that the cell produces. This project involves using this system to assay mutagenesis and survival to establish that Lon’s role is in protecting mtDNA from mutations that are caused by DNA damage. The goal of this research is to help us better understand how Lon preserves mtDNA integrity and mitochondrial function in the face of damaging agents.