Associate ProfessorMatthew McKenzie

Mitochondria are the 'powerhouses' of eukaryotic cells, oxidizing sugars and fats to generate the energy molecule adenosine-5'-triphosphate (ATP). Defects in mitochondrial function can cause disease in both children and adults, which in many cases is fatal. Tissues with high energy demand, such as brain, heart and liver, are commonly affected, with few therapies available for treatment.
Dr McKenzie's research aims to define the pathological mechanisms which underlie these diseases, in particular how disruption of mitochondrial fatty acid beta-oxidation (FAO) and oxidative phosphorylation (OXPHOS) contribute to mitochondrial dysfunction. Dr McKenzie's group is defining the important physical interactions betweenFAO and OXPHOS protein complexes and determining how their disruption contributes to mitochondrial disease pathology. They are also investigating the role that various FAO proteins play in the biogenesis and assembly of the OXPHOS complexes. To do this, they use techniques such as Blue Native-PAGE, in vitro mitochondrial import and protein assembly assays. His group has also developed novel human models of FAO disease by reprogramming patient fibroblasts into induced pluripotent stem (iPS) cells and by CRISPR gene disruption in human ES cells. These stem cell lines can be differentiated into neurons, cardiomyocytes and hepatocytes to model mitochondrial disease pathology in a cell-type specific manner.

Knowledge Areas
Mitochondrial biology; Mitochondrial Disease; Oxidative Phosphorylation; Fatty acid oxidation; Stem Cells

Projects
Developing new stem cell models to investigate how defects in fatty acid oxidation contribute to human mitochondrial disease

Defining how microRNAs regulate mitochondrial metabolism

Developing novel therapeutic compounds for treating mitochondrial disease