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What is driving clonal expansion of mitochondrial DNA deletions?


Amy Vincent

Newcastle University

United Kingdom

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.