Investigating Pathogenesis Associated with Dysfunctional Mitochondrial Protein Import

PhD Top-up Scholarships

$18,000 AUD

08/01/2018 → 08/01/2021

Carolyn Sue


Thomas Jackson


Dr Diana Stojanovski

Project Name

Investigating Pathogenesis Associated with Dysfunctional Mitochondrial Protein Import

Project Details

Understanding how mitochondria work is the key to finding treatments and cures for the many types of mitochondrial diseases (mito). Tom Jackson’s project focuses on increasing knowledge about a specific molecular component within mitochondria and its impact on patients with Sengers syndrome, a severe type of mito.

Inside the power plant of the mitochondrion is a workforce known as ‘proteins’. These proteins perform many critical functions of mitochondria. In healthy human cells about 1500 proteins must be moved to their correct location within mitochondria. If the process of ‘protein import’ fails to occur, the energy and production and general mitochondrial function is affected.

Thomas’ project focusses on a tiny molecular machine, the TIM22. 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 form of mito. AGK helps to import carrier proteins into mitochondria, but also produces important lipid molecules that help mitochondria function normally.

The aim of this study is to uncover if and how the two seemingly distinct functions of AGK result in mitochondrial disease. As part of his project, Thomas will undertake characterisation of AGK’s functions and interactions in healthy and patient cells to understand how AGK function is manipulated during mito.

Research Update – January 2019

Through his PhD Top-Up Scholarship from The Mito Foundation and with the help of a Canadian hospital, Thomas received cells from a patient with a new mutation in AGK and an unusual form of Sengers syndrome. By studying these cells, along with cells from two patients with more typical Sengers syndrome, Thomas’s lab has made some interesting discoveries.

One such discovery is that defects in mitochondrial import machineries are increasingly being identified as causes of mito, and in October 2018 Thomas’s lab published a review article in Biochemical Society Transactions describing their current understanding of how mutations in import machinery components can lead to mito.

This research will see Thomas present a short talk at the upcoming EMBO protein translocation workshop in Spain. This will help promote the work Thomas is doing to understand Mito as well as lead to some international collaborations.

Thomas has extended his research to look into another protein import component, Tim50, which also causes Mito when mutated. This new research will look to remove Tim50 from cells to better understand how it functions in health and disease.