Investigating pathogenesis associated with dysfunctional mitochondrial protein import

PhD Top-up Scholarships

$18,000 AUD

01/08/2018 → 01/08/2021

Carolyn Sue


Thomas Daniel Jackson


The University of Melbourne


Dr Diana Stojanovski

Project Name

Investigating pathogenesis associated with dysfunctional mitochondrial protein import

Project Details

The mitochondrion is the cell’s power plant, where sugars from the food we eat are converted into energy that our bodies need to survive. Inside this power plant is a workforce of ‘proteins’ that perform that many critical functions of mitochondria. In healthy human cells about 1500 proteins must be moved to their correct location within mitochondria. This process is known as ‘protein import’, and if it fails to occur correctly energy production and general mitochondrial function is affected.

Import of mitochondrial proteins is carried out by tiny machines called translocases. My project focusses on one of these tiny molecular machines, the TIM22 complex. TIM22 is involved in the import of a group of tunnel-like proteins, known as carrier proteins, which are critical for normal mitochondrial energy production. One component of TIM22, called AGK, is mutated in patients with Sengers syndrome, a severe mitochondrial disease. AGK helps to import carrier proteins into mitochondria, but also produces important lipid molecules that help mitochondria function normally. I will study AGK mutations to uncover if and how the two seemingly distinct functions of AGK result in mitochondrial disease. Furthermore, as part of my project we will undertake the ambitious task of determining the 3D shape of AGK using a technique called X-ray crystallography. Understanding the shape of AGK will help to understand how it functions normally and how this function is disrupted during mitochondrial disease.