Stroud laboratory: Mitochondrial Systems Biology

Researcher

Research Overview

Mitochondria are the main source of energy in eukaryotic cells, oxidizing sugars and fats to generate ATP through oxidative phosphorylation (OXPHOS), which is accomplished by the respiratory chain (Figure 1). Defects in OXPHOS affect the respiratory chain and lead to classical childhood mitochondrial disease, which has an incidence of at least ~1/5000 live births. Organs with the highest energy demand such as brain and heart are normally affected, although the disease can affect any organ system alone or in combination. Mutations in almost 200 genes cause mitochondrial disease.

Diagnostic approaches typically focus on known mitochondrial disease genes, whereas the genetic complexity of the disease means drugs targeting one OXPHOS system often fail when another is defective. Functionalisation of the mitochondrial proteome is therefore crucial for improving diagnostic and treatment outcomes.

To functionalise the mitochondrial proteome we apply cutting-edge systems biology approaches, incorporating extensive gene-editing and proteomics tools, as well as classical biochemical, molecular and cell biology techniques.

schematic representation of OXPHOS and the mitochondrial respiratory chain
Figure 1: OXPHOS and the mitochondrial respiratory chain

Staff

Dr Joanna Sacharz, Post doctoral fellow
Dr Boris Reljić, Post doctoral fellow
Ms Daniella Hock, PhD student

Collaborators

Professor Mike Ryan, Department of Biochemistry and Molecular Biology, Monash University
Professor David Thorburn, Murdoch Children's Research Institute
Dr Dianna Stojanovski, Department of Biochemistry and Molecular Biology, The University of Melbourne
Dr Michael Lazarou, Department of Biochemistry and Molecular Biology, Monash University
Dr Rajesh Ghai, Institute for Molecular Bioscience, The University of Queensland

Funding

NHMRC Project Grant (2018-2020):  "Systems approaches to understanding the assembly of mitochondrial machines"
NHMRC Project Grant (2017-2019): "Assembly and mis-assembly of mitochondrial respiratory chain Complex I"
NHMRC Project Grant (2016-2020): "Personalised Medicine for Mitochondrial Disorders: Targeting Pathogenic Mechanisms"
ARC Discovery Project (2016-2018): "Understanding how mitochondria divide"

Research Publications

Click here for the results of a Google Scholar analysis of David's publications.

  1. Höhr AIC, Lindau C, Wirth C, Qiu J, Stroud DA, Kutik S, Guiard B, Hunte C, Becker T, Pfanner N, Wiedemann, N. Membrane protein insertion through a mitochondrial β-barrel gate. Science 2018; 359(6372)
  2. Lake NJ, Webb BD, Stroud DA, Richman TR, Ruzzenente B, Compton AG, Mountford HS, Pulman J, Zangarelli C, Rio M, Bodaert N, Assouline Z, Sherpa MD, Schadt EE, Houten SM, Byrnes J, McCormick EM, Zolkipli-Cunningham Z, Haude K, Zhang Z, Retterer K, Bai R, Calvo SE, Mootha VK, Christodoulou J, Rötig A, Filipovska A, Cristian I, Falk MJ, Metodiev MD, Thorburn DR. Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome. Am J Hum Genet 2017; 101(2): 239-254.
  3. Formosa LE, Dibley MG, Stroud DA, Ryan MT. Building a complex complex: Assembly of mitochondrial respiratory chain complex I. Semin Cell Dev Biol 2017; S1084-9521(17)30019-8
  4. Kang Y, Stroud DA, Baker MJ, De Souza DP, Frazier AE, Liem M, Tull D, Mathivanan S, McConville MJ, Thorburn DR, Ryan MT, Stojanovski D. Sengers Syndrome-Associated Mitochondrial Acylglycerol Kinase Is a Subunit of the Human TIM22 Protein Import Complex. Mol Cell 2017; 67(3): 457-470.
  5. Dibley MG, Ryan MT, Stroud DA. A novel isoform of the human mitochondrial complex I subunit NDUFV3. FEBS Lett 2017; 591(1): 109-117.
  6. Stroud DA, Surgenor EE, Formosa LE, Reljic B, Frazier AE, Dibley MG, Osellame LD, Stait T, Beilharz TH, Thorburn DR, Salim A, Ryan MT. Accessory subunits are integral for assembly and function of human mitochondrial complex I. Nature 2016; 538(7623): 123-126.
  7. Reljić B, Stroud DA. Screening Strategies for TALEN-Mediated Gene Disruption. Methods Mol Biol 2016; 1419: 231-252.
  8. Osellame LD, Singh AP, Stroud DA, Palmer CS, Stojanovski D, Ramachandran R, Ryan MT. Cooperative and independent roles of the Drp1 adaptors Mff, MiD49 and MiD51 in mitochondrial fission. J Cell Sci 2016; 129(11): 2170-2181.
  9. Stroud DA, Maher MJ, Lindau C, Vögtle FN, Frazier AE, Surgenor E, Mountford H, Singh AP, Bonas M, Oeljeklaus S, Warscheid B, Meisinger C, Thorburn DR, Ryan MT. OA6 is a mitochondrial complex IV assembly factor critical for biogenesis of mtDNA-encoded COX2. Hum Mol Genet 2015; 24(19): 5404-5415.
  10. Stroud DA, Formosa LE, Wijeyeratne XW, Nguyen TN, Ryan MT. Gene knockout using transcription activator-like effector nucleases (TALENs) reveals that human NDUFA9 protein is essential for stabilizing the junction between membrane and matrix arms of complex I. J Biol Chem 2013 288(3): 1685-1690.

Research Projects



Faculty Research Themes

Child Health

School Research Themes

Cardio-Respiratory, Systems Biology, Molecular Mechanisms of Disease



Key Contact

For further information about this research, please contact Head of Research Group Dr David Stroud

Department / Centre

Biochemistry and Molecular Biology

Unit / Centre

Stroud laboratory: Mitochondrial Systems Biology


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