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Amino Acid Starvation Has Opposite Effects on Mitochondrial and Cytosolic Protein Synthesis

Johnson, MA; Vidoni, S; Durigon, R; Pearce, SF; Rorbach, J; He, J; Brea-Calvo, G; ... Spinazzola, A; + view all (2014) Amino Acid Starvation Has Opposite Effects on Mitochondrial and Cytosolic Protein Synthesis. PLOS ONE , 9 (4) , Article e93597. 10.1371/journal.pone.0093597. Green open access

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Abstract

Amino acids are essential for cell growth and proliferation for they can serve as precursors of protein synthesis, be remodelled for nucleotide and fat biosynthesis, or be burnt as fuel. Mitochondria are energy producing organelles that additionally play a central role in amino acid homeostasis. One might expect mitochondrial metabolism to be geared towards the production and preservation of amino acids when cells are deprived of an exogenous supply. On the contrary, we find that human cells respond to amino acid starvation by upregulating the amino acid-consuming processes of respiration, protein synthesis, and amino acid catabolism in the mitochondria. The increased utilization of these nutrients in the organelle is not driven primarily by energy demand, as it occurs when glucose is plentiful. Instead it is proposed that the changes in the mitochondrial metabolism complement the repression of cytosolic protein synthesis to restrict cell growth and proliferation when amino acids are limiting. Therefore, stimulating mitochondrial function might offer a means of inhibiting nutrient-demanding anabolism that drives cellular proliferation.

Type: Article
Title: Amino Acid Starvation Has Opposite Effects on Mitochondrial and Cytosolic Protein Synthesis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0093597
Publisher version: http://doi.org/10.1371/journal.pone.0093597
Language: English
Additional information: © 2014 Johnson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: http://discovery.ucl.ac.uk/id/eprint/1546412
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