INCUBATOR GRANT PROJECT

To ensure the efficient supply of energy, mitochondria must maintain a production line of energy-generating machines that are each made up of multiple protein components. Most of these protein components are produced by the cell outside of mitochondria, in the cytosol, and are then imported into mitochondria and assembled into their respective machine. If there are defects in these protein components, energy production is compromised and mitochondrial disease occurs.

The supply line of protein components for delivery into mitochondria is very carefully controlled in order to meet mitochondrial demands without resulting in an excess. The system that controls this supply line is known as the ubiquitin system and it does so by tagging, or untagging, protein components with specific signals made up of ubiquitin molecules. These signals determine the fate of a tagged protein. Tweaking this control system to adjust protein supply into mitochondria, may provide a novel strategy to manipulate mitochondria to produce more energy, thereby overcoming the symptoms of mitochondrial disease. This project aims to investigate how the ubiquitin signalling system regulates mitochondrial proteins on their journey from the cytosol to the mitochondria. The ubiquitin system is currently the focus of drug development for a range of diseases and the ultimate goal is to determine whether such drugs could also have potential for treating mitochondrial disease.