Investigation of the mitochondrial DNA heteroplasmy in the context of DNA damage and repair - WCUB, BfH, ENWW

Mitochondria are small double--membrane bound organelles found at high copy numbers within all eukaryotic cells. Mitochondria are the main component of the cell energy metabolism where oxidative phosphorylation (OXPHOS) takes place within cells; they are also involved in calcium ion flux regulation, apoptosis regulation, and intracellular signalling. Mitochondria contain hundreds of copies of their own small circular genomes that are indispensable to the organelle function and that encode numerous RNA molecules as well as several protein components of the OXPHOS electron transport chain machinery. Mitochondrial genome changes are associated with aging and disease states such as cancer. In humans, the mitochondrial genome is roughly 16.5kb long and normally shows a low level sequence variation between otherwise identical copies, known as heteroplasmy. Upon certain types of DNA damage, as well as in cancers, some of this low-level variation becomes enhanced. We speculate that the low-level sequence variation observed may be linked with an on-going balance between mitochondrial DNA damage and repair, and may be indicative of the baseline activity of the different repair mechanisms taking place in the mitochondria. Therefore we aim to investigate this low-level sequence variability to determine its causes and effects on cell function. A better understanding of this phenomenon will provide us with insights into fundamental mitochondrial biology, mitochondrial DNA repair mechanisms, and the importance of the mitochondria as the sources of retrograde signalling within cells via small peptides and other signal carriers.

BBSRC research priority areas Data driven biology, healthy ageing across the lifecourse, exploiting new ways of working