Molecular Basis of Mitochondrial Disease

Molecular Basis of Mitochondrial Disease Research Group

Mitochondria are the ‘powerhouses’ of eukaryotic cells, oxidising sugars and fats to generate energy. Defects in mitochondrial function can cause disease in both children and adults, and commonly affects high-energy demand tissues such as brain, heart, and liver. Unfortunately, there are no effective therapies to treat mitochondrial disorders and in many cases the disease is fatal.

Dr McKenzie’s research aims to define the pathological mechanisms which underlie these diseases by investigating the physical interactions between mitochondrial fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS) protein complexes. His group is determining how disruption of these important interactions contributes to mitochondrial disease pathology by using techniques such as Blue Native-PAGE and in vitro mitochondrial import assays. His team is also developing new human models of mitochondrial disease by reprogramming patient fibroblasts into induced pluripotent stem (iPS) cells and novel mouse models using ‘cybrid’ fusion technology.

See how Dr McKenzie’s research team measure mitochondrial calcium and mitochondrial membrane potential using confocal microscopy in their video published in Journal of Visualized Experiments.

Research Projects

Research Group

Selected publications

  • Lim SC, Hroudova J, Van Bergen NJ, Lopez Sanchez MI, Trounce IA, McKenzie M (2016) Loss of mitochondrial DNA-encoded protein ND1 results in disruption of complex I biogenesis during early stages of assembly. FASEB J 30:2236-2248.

  • Cagnone GL, Tsai TS, Makanji Y, Matthews P, Gould J, Bonkowski MS, Elgass KD, Wong AS, Wu LE, McKenzie M, Sinclair DA, St John JC (2016) Restoration of normal embryogenesis by mitochondrial supplementation in pig oocytes exhibiting mitochondrial DNA deficiency. Sci Rep 6:23229.

  • Lim SC, Carey KT, McKenzie M (2015) Anti-Cancer analogues ME-143 and ME-344 exert toxicity by directly inhibiting mitochondrial NADH:ubiquinone oxidoreductase (Complex I). Am J Cancer Res 5:689-701.

  • McKenzie M, Chiotis M, Hroudova J, Sanchez MI, Lim SC, Cook MJ, McKelvie P, Cotton RG, Murphy M, St John JC, Trounce IA (2014) Capture of Somatic mtDNA Point Mutations with Severe Effects on Oxidative Phosphorylation in Synaptosome Cybrid Clones from Human Brain. Hum Mutat 35:1476-1484.

  • Trounce IA, Crouch PJ, Carey KT, McKenzie M (2013) Modulation of ceramide-induced cell death and superoxide production by mitochondrial DNA-encoded respiratory chain defects in Rattus xenocybrid mouse cells. Biochim Biophys Acta 1827:817-825.