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Peroxisomal compartmentalization of amino acid biosynthesis reactions imposes an upper limit on compartment size

Ying Gu, Sara Alam, View ORCID ProfileSnezhana Oliferenko
doi: https://doi.org/10.1101/2023.03.06.531353
Ying Gu
1The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK
2Randall Centre for Cell and Molecular Biophysics, School of Basic and Medical Biosciences, King’s College London, London, SE1 1UL, UK
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  • For correspondence: ying.1.gu@kcl.ac.uk snezhka.oliferenko@crick.ac.uk
Sara Alam
1The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK
2Randall Centre for Cell and Molecular Biophysics, School of Basic and Medical Biosciences, King’s College London, London, SE1 1UL, UK
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Snezhana Oliferenko
1The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK
2Randall Centre for Cell and Molecular Biophysics, School of Basic and Medical Biosciences, King’s College London, London, SE1 1UL, UK
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  • ORCID record for Snezhana Oliferenko
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Summary

Cellular metabolism relies on just a few redox cofactors. Selective compartmentalization may prevent competition between metabolic reactions requiring the same cofactor. Is such compartmentalization necessary for optimal cell function? Is there an optimal compartment size? Here we probe these fundamental questions using peroxisomal compartmentalization of the last steps of lysine and histidine biosynthesis in the fission yeast Schizosaccharomyces japonicus. We show that compartmentalization of these NAD+ dependent reactions together with a dedicated NADH/NAD+ recycling enzyme supports optimal growth when an increased demand for anabolic reactions taxes cellular redox balance. In turn, compartmentalization constrains the size of individual organelles, with larger peroxisomes accumulating all the required enzymes but unable to support both biosynthetic reactions at the same time. We propose that compartmentalized biosynthetic reactions are sensitive to the size of the compartment, likely due to scaling-dependent changes within the system, such as enzyme packing density.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵3 Co-corresponding authors.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted March 07, 2023.
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Peroxisomal compartmentalization of amino acid biosynthesis reactions imposes an upper limit on compartment size
Ying Gu, Sara Alam, Snezhana Oliferenko
bioRxiv 2023.03.06.531353; doi: https://doi.org/10.1101/2023.03.06.531353
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Peroxisomal compartmentalization of amino acid biosynthesis reactions imposes an upper limit on compartment size
Ying Gu, Sara Alam, Snezhana Oliferenko
bioRxiv 2023.03.06.531353; doi: https://doi.org/10.1101/2023.03.06.531353

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