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Peroxisomal compartmentalization of amino acid biosynthesis reactions imposes an upper limit on compartment size
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Peroxisomal compartmentalization of amino acid biosynthesis reactions imposes an upper limit on compartment size
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Journal Article
Peroxisomal compartmentalization of amino acid biosynthesis reactions imposes an upper limit on compartment size
2023
Overview
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. Our reengineering and physiological experiments indicate 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.
Compartmentalization is thought to modulate metabolic flux by spatially segregating enzymes and their coupled reactants. Here, the authors show that peroxisomal compartmentalization of amino acid synthesis imposes an upper limit on compartment size.
