Stojanovski Laboratory: Mitochondrial Biogenesis in Health and Disease

Research Overview

The Stojanovski Lab is working as part of a global effort to understand the inner workings of one of the cells most intriguing and important organelles, the Mitochondrion (Figure 1).

Mitochondria are essential compartments in all of our cells involved in the generation of ATP, the energy currency of life. Mitochondria also serve as sensor for multiple metabolic functions and are key players in health and disease. Organelle dysfunction is linked to diseases, including cancer, Alzheimer’s and Parkinson’s disease; and numerous intracellular pathogens often target proteins to mitochondria to modulate the function of the organelle.

Mitochondria cannot be created de novo and are created through a process of biogenesis and division. This genesis requires the coordinated synthesis and assembly of both proteins and lipids that make up the organelle.

Our research aims to:

  1. understand the machineries and mechanisms that drive mitochondrial protein biogenesis in human cells;
  2. investigate the link between defects in mitochondrial protein biogenesis and human disease, and
  3. uncover how pathogens modulate mitochondrial function through the targeting of effector proteins to the organelle.

photomicrograph showing mitochondria

Figure 1: Mitochondria in a HeLa cell (shown in yellow) radiate out from the nucleus (shown in blue) and form a reticular network.

Staff

Yi Lin Kang, PhD Student
Laura Fielden, Honours Student
Lara Freeman, Honours Student
David Gillett, Honours Student

photo of Stojanovski staff

Collaborators

Dr Hayley Newton, Department of Microbiology and Immunology, Doherty Institute, The University of Melbourne

Research Publications

Complete listing of Dr Diana Stojanovski' publications.

Dr Diana Stojanovski - Google Scholar

  • Holloway G, Jognson RI, Kang Y, Dang VT, Stojanovski D, Coulson BS.  Rotavirus NSP6 localizes to mitochondria via a predicted N-terminal α-helix. J Gen Vir 2015 (Accepted 19 September 2015).
  • Baker MJ, Lampe P, Stojanovski D, Korwitz A, Ruchika A, Tatsuta T, Langer T.  Stress-induced OMA1 activation and autocatalytic turnover regulates OPA1-dependent mitochondrial dynamics. EMBO J 2014; 33: 578-593.
  • Baker MJ, Palmer CS, Stojanovski D.*  Mitochondrial protein quality control in health and disease. British Journal of Pharmacology, Themed Issue, Mitochondrial Pharmacology – Energy, Injury and Beyond. 2013; 171: 1870 – 1889.

    *corresponding author
  • Palmer CS, Elgass KD, Parton RG, Osellame LD, Stojanovski D, Ryan MT.  MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and are specific for mitochondrial fission. J Biol Chem 2013; 288: 27584 – 27593.
  • Varabyova A, Stojanovski D, Chacinska A.  Mitochondrial protein homeostasis. IUBMB Life 2013; 65: 191-201.
  • Baker MJ, Mooga VP, Guiard B, Langer T, Ryan MT*, Stojanovski D. * Impaired folding of the mitochondrial small TIM chaperones induces clearance by the i-AAA protease. J Mol Biol 2012; 424: 227-239.

    *corresponding author
  • Ryan MT, Stojanovski D. Mitofusins “bridge” the gap between oxidative stress and mitochondrial hyperfusion. EMBO Rep 2012; 13: 870-871.
  • Stojanovski D, Bragoszewski P, Chacinska A.  The MIA pathway: A tight bond between protein transport and oxidative  folding in mitochondria. BBA Mol. Cell Res 2012; 1823: 1142-1150.
  • Palmer CS, Osellame LD, Stojanovski D, Ryan MT.  The regulation of mitochondrial morphology: Intricate mechanisms and dynamic machinery. Cell Signal 2011; 23: 1534-1545.
  • Stroud D, Becker T, Qui J, Stojanovski D, Pfannschmidt S, Wirth C, Hunte C, Guiard B, Meisinger C, Pfanner N, Wiedemann N.  Biogenesis of mitochondrial β-barrel proteins: the POTRA domain is involved in precursor release from the SAM complex. Mol Biol Cell 2011; 22: 2823-2833.
  • Schmitdt O, Harbauer AB, Rao S, Eyrich B, Zahedi RP, Stojanovski D, Schönfisch B, Guiard B, Sickmann A, Pfanner N, Meisinger C.  Regulation of mitochondrial preprotein translocase by casein kinase 2 and protein kinase A. Cell 2011; 144: 227-239.
  • Gebert N, Ryan MT, Pfanner N, Wiedemann N, Stojanovski D.  Mitochondrial protein import machineries and lipids: A functional connection. BBA Biomembranes 2011; 1808: 1002-1011.
  • Lazarou M*, Stojanovski D*, Frazier AE, Kotevski A, Dewson G, Craigen WJ, Kluck RM, Vaux DL, Ryan MT.  Inhibition of Bak activation by VDAC2 is dependent on the Bak transmembrane anchor. J Biol Chem 2010; 285: 36876-36883.

    *equally contributing
  • Milenkovic D, Ramming T, Müller JM, Wenz L-S, Gebert N, Stojanovski D, Rospert S, Chacinska A. Identification of the signal directing proteins into the intermembrane space of mitochondria. Mol Biol Cell 2009; 20: 2530-2539.
  • Stojanovski D*, Milenkovic D*, Müller JM, Gabriel K, Schulze-Specking A, Baker MJ, Ryan MT, Guiard B, Pfanner N, Chacinska A.  Mitochondrial protein import: precursor oxidation in a ternary complex with disulfide carrier and sulfhydryl oxidase. J Cell Biol 2008; 183: 195-202.

    *equally contributing
  • Kutik S, Stojanovski D, Becker T, Stroud DA, Becker L, Meinecke M, Krüger V, Prinz C, Guiard B, Wagner R, Meisinger C, Pfanner N, Wiedemann N.  Authors Response: The mitochondrial β-signal and protein sorting. Cell 2008; 135: 1059-1060.
  • Kutik S, Stojanovski D, Becker L, Becker T, Meinecke M, Krüger V, Prinz C, Meisinger C, Guiard B, Wagner R, Pfanner N, Wiedemann N.  Dissecting membrane insertion of mitochondrial beta-barrel proteins. Cell 2008; 132: 1011-1024.
  • Becker T, Vögtle F-N, Stojanovski D, Meisinger C.  Sorting and assembly of mitochondrial outer membrane proteins. BBA Bioenergetics 2008; 1777: 557-563.
  • Stojanovski D, Müller M, Milenkovic D, Pfanner N, Chacinska A. The MIA system for protein import into the mitochondrial intermembrane space. BBA Mol Cell Res 2008; 1783: 610-617.
  • Becker T, Pfannschmidt S, Guiard B, Stojanovski D, Milenkovic D, Kutik S, Pfanner N, Meisinger C, Wiedemann N.  Biogenesis of the mitochondrial TOM complex: Mim1 promotes insertion and assembly of signal anchored receptors. J Biol Chem 2008; 283: 120-127.
  • Stojanovski D, Guiard B, Kozjak-Pavlovic V, Pfanner N, Meisinger C.  Alternative function for the mitochondrial SAM complex in biogenesis of α-helical TOM proteins. J Cell Biol 2007;179: 881-893.
  • Reinders J, Wagner K, Zahedi RP, Stojanovski D, Eyrich B, van der Laan M, Rehling P, Sickmann A, Pfanner N, Mesinger C.  Profiling phosphoproteins of yeast mitochondria reveals a role of phosphorylation in assembly of the ATP synthase. Mol Cell Prot 2007; 6: 1896-1906.
  • Milenkovic D, Müller M, Stojanovski D, Pfanner N, Chacinska A.  Diverse mechanisms and machineries for import of mitochondrial proteins. Biol Chem 2007; 388: 891-897.
  • Meisinger C, Pfannschmidt S, Rissler M, Milenkovic D, Becker T, Stojanovski D, Youngman MJ, Jensen RE, Chacinska A, Guiard B, Pfanner N, Wiedemann N.  The morphology proteins Mdm12/Mmm1 function in the major beta-barrel assembly pathway of mitochondria. EMBO J 2007; 26: 2229-2239.
  • Stojanovski D, Rissler M, Pfanner N, Meisinger C.  Mitochondrial morphology and protein import- a tight connection? BBA Mol Cell Res 2006; 1763: 414-421.
  • Frazier AE,  Kiu C, Stojanovski D, Hoogenraad NJ, Ryan MT.  Mitochondrial morphology and distribution in mammalian cells. Biol Chem 2006; 387: 1551-1558.
  • Humphries AD, Streimann IC, Stojanovski D, Johnston AJ, Yano M, Hoogenraad NJ, Ryan MT.  Dissection of the mitochondrial import and assembly pathway for human Tom40. J Biol Chem 2005; 80: 11535-11543.
  • Stojanovski D, Koutsopoulos OS, Okamoto K, Ryan MT.  Levels of human Fis1 at the mitochondrial outer membrane regulate mitochondrial morphology. J Cell Sci 2004; 117: 1201-1210.
  • Stojanovski D, Johnston AJ, Streinmann I, Hoogenraad NJ, Ryan MT.  Import of nuclear encoded proteins into mitochondria. Exper Phys 2003; 88: 57-64.

Book Chapters

  • Stojanovski D, Bohnert M, Pfanner N, van der Laan M.  Mechanisms of Protein Sorting in Mitochondria. Cold Spring Harbor Perspectives in Biology 2012; 4 (10).
  • Stojanovski D, Pfanner N, Wiedemann N.  Protein import into mitochondria. Meth Cell Biol 2007; 80: 783-806.

Research Projects



Faculty Research Themes

Cancer, Infection and Immunology

School Research Themes

Cancer, Infection & Immunity, Molecular Mechanisms of Disease



Key Contact

For further information about this research, please contact Dr Diana Stojanovski

Department / Centre

Biochemistry and Molecular Biology