How mtDNA Mutations Cause Mitochondrial Disease

Mutations in the mitochondrial genome (mtDNA) cause devastating diseases with a myriad of clinical features. Tissues with high energetic demands including the brain, liver, muscle, and heart are particularly vulnerable to mtDNA mutations. Majority of mtDNA diseases are caused by heteroplasmic mutations, Heteroplasmy refers to a state in which mutant mtDNA coexists with wildtype mtDNA in the same cell. Heteroplasmic mtDNA mutations cause disease then their level exceeds a critical threshold (typically 60-80 percent). While it is known that mutant mtDNA levels can vary between tissues, the underlying mechanisms are not known. In this project, we seek to develop C. elegans as a model system to study how mutant mtDNA levels can vary across different cell types. Below I detail the progress we have made on this project since the submission of the last progress report.