The nuclear supervision of mitochondrial DNA transmission

A small subset of our DNA is maintained in a structure called mitochondrion, the energy producing organelle. Mitochondrial DNA (mtDNA) has a great impact on health and mutations are linked to various incurable diseases and ageing. Individual cells have many copies of mtDNA, so damaged DNA often co-exist with healthy copies. During development and ageing, as mtDNA continues to replicate, damaged ones can outcompete healthy copies to increase their abundance and cause disease. Yet, little is known about how co-existing mtDNA compete for transmission to impact disease progression. After establishing powerful systems in fruitflies and cultured cells, we screened thousands of nuclear genes and compounds to identify regulators of mtDNA competition. We will finalise the screens and perform detailed studies on identified candidates to elucidate underlying mechanisms. This work will reveal molecular rules governing mtDNA transmission and lead to interventions that alleviate mitochondrial disease and age-related declines in mtDNA quality.