Amino acid starvation has opposite effects on mitochondrial and cytosolic protein synthesis.

TitleAmino acid starvation has opposite effects on mitochondrial and cytosolic protein synthesis.
Publication TypeJournal Article
Year of Publication2014
AuthorsJohnson, MA, Vidoni, S, Durigon, R, Pearce, SF, Rorbach, J, He, J, Brea-Calvo, G, Minczuk, M, Reyes, A, Holt, IJ, Spinazzola, A
JournalPLoS One
Volume9
Issue4
Paginatione93597
Date Published2014
ISSN1932-6203
KeywordsAmino Acids, Cell Respiration, Cytosol, HEK293 Cells, Humans, Membrane Potential, Mitochondrial, Mitochondria, Mitochondrial Proteins, Mitochondrial Turnover, Protein Biosynthesis, RNA, Messenger
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.

DOI10.1371/journal.pone.0093597
Alternate JournalPLoS ONE
Citation Key10.1371/journal.pone.0093597
PubMed ID24718614
PubMed Central IDPMC3981720
Grant ListMC_UP_1002/1 / / Medical Research Council / United Kingdom
MC_U105663140 / / Medical Research Council / United Kingdom
MC_U105697134 / / Medical Research Council / United Kingdom
MC_PC_13029 / / Medical Research Council / United Kingdom
MC_UP_1202/14 / / Medical Research Council / United Kingdom
MC_U105697135 / / Medical Research Council / United Kingdom