Dr Matthew McKenzie


Following the completion of his PhD in 2002, Dr Matthew McKenzie undertook his postdoctoral research in the laboratory of Professor Michael Duchen, University College London. There he investigated how mitochondrial membrane potential, calcium handling and ATP generation are disrupted in mitochondrial disorders using state-of-the-art confocal imaging techniques.

In 2004, Dr McKenzie returned to Australia to work in Professor Michael Ryan’s laboratory at Melbourne’s La Trobe University. During this time, he received an NHMRC Peter Doherty Fellowship, and subsequently an NHMRC Career Development Fellowship, to study the biogenesis of mitochondrial complex I and how inherited defects can disrupt this process.

In April 2011, Hudson Institute of Medical Research recruited Dr McKenzie as a Research Group Leader in the Centre for Genetic Diseases. His current research focuses on interactions between protein complexes involved in mitochondrial fatty acid beta-oxidation (FAO) and oxidative phosphorylation (OXPHOS), and their importance in human disease pathology. The Australian Research Council recently recognised Dr McKenzie’s research excellence with a prestigious Future Fellowship. Additionally, he also receives support from the Australian Mitochondrial Disease Foundation, the William Buckland Foundation, Marshall Edwards Inc., USA, and Monash University.

Selected publications

  • Lim SC, Smith KR, Stroud DA, Compton AG, Tucker EJ, Dasvarma A, Gandolfo LC, Marum JE, McKenzie M, Peters HL, Mowat D, Procopis PG, Wilcken B, Christodoulou J, Brown GK, Ryan MT, Bahlo M, Thorburn DR (2014) A founder mutation in PET100 causes isolated complex IV deficiency in Lebanese individuals with Leigh syndrome. Am J Hum Genet 94:209-222.

  • Yeung KY, Dickinson A, Donoghue JF, Polekhina G, White SJ, Grammatopoulos DK, McKenzie M, Johns TG, St John JC (2014) The identification of mitochondrial DNA variants in glioblastoma multiforme. Acta Neuropathol Commun 2:1.

  • Dickinson A, Yeung KY, Donoghue J, Baker MJ, Kelly RD, McKenzie M, Johns TG, St John JC (2013) The regulation of mitochondrial DNA copy number in glioblastoma cells. Cell Death Differ 20:1644-1653.

  • Kelly RD, Rodda AE, Dickinson A, Mahmud A, Nefzger CM, Lee W, Forsythe JS, Polo JM, Trounce IA, McKenzie M, Nisbet DR, St John JC (2013) Mitochondrial DNA haplotypes define gene expression patterns in pluripotent and differentiating embryonic stem cells. Stem Cells 31:703-716.

  • McKenzie M (2013) Mitochondrial DNA mutations and their effects on complex I biogenesis: implications for metabolic disease. In Mitochondrial DNA, Mitochondria, Disease and Stem Cells. St John JC, ed. New York: Humana Press. pp 25-47.

  • 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.

  • Kelly RD, Mahmud A, McKenzie M, Trounce IA, St John JC (2012) Mitochondrial DNA copy number is regulated in a tissue specific manner by DNA methylation of the nuclear-encoded DNA polymerase gamma A. Nucleic Acids Res 40:10124-10138.

  • Leong DW, Komen JC, Hewitt CA, Arnaud E, McKenzie M, Phipson B, Bahlo M, Laskowski A, Kinkel SA, Davey GM, Heath WR, Voss AK, Zahedi RP, Pitt JJ, Chrast R, Sickmann A, Ryan MT, Smyth GK, Thorburn DR, Scott HS (2012) Proteomic and metabolomic analyses of mitochondrial complex I-deficient mouse model generated by spontaneous B2 short interspersed nuclear element (SINE) insertion into NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) gene. J Biol Chem 287:20652-20663.

  • Tucker EJ, Mimaki M, Compton AG, McKenzie M, Ryan MT, Thorburn DR (2012) Next-generation sequencing in molecular diagnosis: NUBPL mutations highlight the challenges of variant detection and interpretation. Hum Mutat 33:411-418.

  • McKenzie M, Tucker EJ, Compton AG, Lazarou M, George C, Thorburn DR, Ryan MT (2011) Mutations in the gene encoding C8orf38 block complex I assembly by inhibiting production of the mitochondria-encoded subunit ND1. J Mol Biol 414:413-426.

  • Tucker EJ, Hershman SG, Kohrer C, Belcher-Timme CA, Patel J, Goldberger OA, Christodoulou J, Silberstein JM, McKenzie M, Ryan MT, Compton AG, Jaffe JD, Carr SA, Calvo SE, RajBhandary UL, Thorburn DR, Mootha VK (2011) Mutations in MTFMT underlie a human disorder of formylation causing impaired mitochondrial translation. Cell Metab 14:428-434.

  • McKenzie M, Ryan MT (2010) Assembly factors of human mitochondrial complex I and their defects in disease. IUBMB Life 62:497-502.

  • Riley LG, Cooper S, Hickey P, Rudinger-Thirion J, McKenzie M, Compton A, Lim SC, Thorburn D, Ryan MT, Giege R, Bahlo M, Christodoulou J (2010) Mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, causes myopathy, lactic acidosis, and sideroblastic anemia-MLASA syndrome. Am J Hum Genet 87:52-59.

  • Gebert N, Joshi AS, Kutik S, Becker T, McKenzie M, Guan XL, Mooga VP, Stroud DA, Kulkarni G, Wenk MR, Rehling P, Meisinger C, Ryan MT, Wiedemann N, Greenberg ML, Pfanner N (2009) Mitochondrial cardiolipin involved in outer-membrane protein biogenesis: implications for Barth syndrome. Curr Biol 19:2133-2139.

  • Lazarou M, Smith SM, Thorburn DR, Ryan MT, McKenzie M (2009) Assembly of nuclear DNA-encoded subunits into mitochondrial complex IV, and their preferential integration into supercomplex forms in patient mitochondria. FEBS J 276:6701-6713.

  • Lazarou M, Thorburn DR, Ryan MT, McKenzie M (2009) Assembly of mitochondrial complex I and defects in disease. Biochim Biophys Acta 1793:78-88.

  • Sugiana C, Pagliarini DJ, McKenzie M, Kirby DM, Salemi R, Abu-Amero KK, Dahl HH, Hutchison WM, Vascotto KA, Smith SM, Newbold RF, Christodoulou J, Calvo S, Mootha VK, Ryan MT, Thorburn DR (2008) Mutation of C20orf7 disrupts complex I assembly and causes lethal neonatal mitochondrial disease. Am J Hum Genet 83:468-478.

  • Dunning CJ*, McKenzie M*, Sugiana C, Lazarou M, Silke J, Connelly A, Fletcher JM, Kirby DM, Thorburn DR, Ryan MT (2007) Human CIA30 is involved in the early assembly of mitochondrial complex I and mutations in its gene cause disease. EMBO J 26:3227-3237. (*joint first authors)

  • Lazarou M, McKenzie M, Ohtake A, Thorburn DR, Ryan MT (2007) Analysis of the assembly profiles for mitochondrial- and nuclear-DNA-encoded subunits into complex I. Mol Cell Biol 27:4228-4237.

  • McKenzie M, Lazarou M, Thorburn DR, Ryan MT (2007) Analysis of mitochondrial subunit assembly into respiratory chain complexes using Blue Native polyacrylamide gel electrophoresis. Anal Biochem 364:128-137.

  • McKenzie M, Liolitsa D, Akinshina N, Campanella M, Sisodiya S, Hargreaves I, Nirmalananthan N, Sweeney MG, Abou-Sleiman PM, Wood NW, Hanna MG, Duchen MR (2007) Mitochondrial ND5 gene variation associated with encephalomyopathy and mitochondrial ATP consumption. J Biol Chem 282:36845-36852.

  • McKenzie M, Lazarou M, Thorburn DR, Ryan MT (2006) Mitochondrial respiratory chain supercomplexes are destabilized in Barth Syndrome patients. J Mol Biol 361:462-469.

  • McKenzie M, Liolitsa D, Hanna MG (2004) Mitochondrial disease: mutations and mechanisms. Neurochem Res 29:589-600.

  • McKenzie M, Trounce IA, Cassar CA, Pinkert CA (2004) Production of homoplasmic xenomitochondrial mice. Proc Natl Acad Sci USA 101:1685-1690.

  • McKenzie M, Chiotis M, Pinkert CA, Trounce IA (2003) Functional respiratory chain analyses in murid xenomitochondrial cybrids expose coevolutionary constraints of cytochrome b and nuclear subunits of complex III. Mol Biol Evol 20:1117-1124.