Journal Article

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

Rorbach, Joanna, Reyes, Aurelio, Holt, Ian J., Durigon, Romina, Brea-Calvo, Gloria, Spinazzola, Antonella, Pearce, Sarah F., Johnson, Mark A., He, Jiuya, Minczuk, Michal, Vidoni, Sara

2014

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Amino acid starvation / Amino acids / Amino Acids - deficiency / Amino Acids - metabolism / Analysis / Biology / Biology and Life Sciences / Biosynthesis / Catabolism / Cell growth / Cell Respiration / Cytosol - metabolism / Deoxyribonucleic acid / DNA / Electron transport / Energy demand / Gene expression / Glucose / HEK293 Cells / Homeostasis / Humans / Kinases / Medical research / Medicine and Health Sciences / Membrane Potential, Mitochondrial / Metabolism / Metabolites / Mitochondria / Mitochondria - metabolism / Mitochondrial DNA / Mitochondrial Proteins - biosynthesis / Mitochondrial Turnover / Nutrients / Organelles / Phosphorylation / Physical Sciences / Physiological aspects / Preservation / Protein Biosynthesis / Protein synthesis / Protein turnover / Proteins / Respiration / RNA, Messenger - genetics / RNA, Messenger - metabolism / Starvation