Systems approaches to understanding the assembly of mitochondrial machines

Identification: Stroud, David


Description

 

Systems approaches to understanding the assembly of mitochondrial machines
 
Stroud D.A.1,* , Formosa L.E.2 , Lake N.J.3 , Thorburn D.R.3 and Ryan M.T.2
1Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Victoria, Australia
2Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia
3Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia
*Corresponding Author
      
We are coupling extensive use of gene-editing technologies with large-scale quantitative proteomics to dissect the structure, function and assembly of multi-subunit membrane complexes in vivo, and discover new proteins regulating their biogenesis. In the first example, I will describe how we applied these tools to investigate human mitochondrial respiratory chain complex I assembly, with a particular focus on the identification of new assembly factors. In the second example, I will introduce our ongoing studies into the biogenesis of the other respiratory chain complexes. Finally, I will describe a mitochondrial disease patient with a novel mitoribosome protein defect, in which we used our proteomics pipeline to identify an instability in the small mitoribosome subunit and respiratory chain complexes I and IV. Our work demonstrates how the coupling of gene-editing technology with large scale proteomics yields a powerful tool for dissecting multi-subunit membrane complexes and enables us to study the impact of their dysfunction at a cellular level.
 

 

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