What is driving clonal expansion of mitochondrial DNA deletions?
Mitochondria fuel all the cells in the body and contain their own mitochondrial DNA (mtDNA). Over 1:5000 people have mtDNA mutations, characterised by large mtDNA deletions, which often cause devastating, untreatable diseases. There are hundreds of mtDNA per cell, so a single deleted mtDNA has little impact. However, mtDNA deletions accumulate throughout life leading to mitochondrial dysfunction.
I have previously found that this accumulation starts close to the nuclei, the cells’ control centre in skeletal muscle. In this project I will use human muscle to study the link between mtDNA deletions, mitochondria to nuclear communication and mitochondrial shape. I will use a mouse model to understand how the replication of mtDNA and the production of new mitochondria affects clonal expansion. I will then jointly grow human muscle and nerve cells in the lab to use as a modifiable model.
This work will help to understand how these diseases arise and progress, leading to future therapy.