18.10.2017 - 16:57
A  A

Impact of tissue-related mtDNA heteroplasmies on mitochondrial function

The mitochondrial DNA (mtDNA) is present in several copies within a single mitochondrium. Furthermore, each cell comprises numerous mitochondria resulting in up to thousands of mtDNA genomes in a single cell. These copies are scarcely completely identical but differ at certain positions in the genome, a state referred to as heteroplasmy. Some heteroplasmic mutations have been linked to diseases such as cancer and they also appear to be associated with aging.

Within the last years it has been highlighted that certain heteroplasmies occur in a tissue-related fashion in humans. In particular, liver or muscle tissues tend to accumulate certain mutations that are not or sparsely present in other tissues. Interestingly, most of these heteroplasmies are found in the non-coding, regulatory control region (CR) of the mitochondrial DNA indicating that the heteroplasmies specifically influence DNA content or transcription efficiency. However, minimal knowledge exists on the impact of these heteroplasmies on mitochondrial function, the single cell behavior and on the whole tissue.

My aim is to investigate the distribution of different mtDNA variants within the cell and the tissue. Furthermore, I intend to investigate the impact of certain tissue-related heteroplasmies on mtDNA maintenance as well as mitochondrial and cellular function.