Amino acid starvation has opposite effects on mitochondrial and cytosolic protein synthesis.
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.
MRC-Mitochondrial Biology Unit, Wellcome Trust-MRC Building, Cambridge, United Kingdom.
Mark A
MA
Johnson
MRC-Mitochondrial Biology Unit, Wellcome Trust-MRC Building, Cambridge, United Kingdom.
Sara
S
Vidoni
NIMR-National Institute for Medical Research, Mill Hill, London, United Kingdom.
Romina
R
Durigon
MRC-Mitochondrial Biology Unit, Wellcome Trust-MRC Building, Cambridge, United Kingdom.
Sarah F
SF
Pearce
MRC-Mitochondrial Biology Unit, Wellcome Trust-MRC Building, Cambridge, United Kingdom.
Joanna
J
Rorbach
MRC-Mitochondrial Biology Unit, Wellcome Trust-MRC Building, Cambridge, United Kingdom.
Jiuya
J
He
MRC-Mitochondrial Biology Unit, Wellcome Trust-MRC Building, Cambridge, United Kingdom.
Gloria
G
Brea-Calvo
MRC-Mitochondrial Biology Unit, Wellcome Trust-MRC Building, Cambridge, United Kingdom.
Michal
M
Minczuk
MRC-Mitochondrial Biology Unit, Wellcome Trust-MRC Building, Cambridge, United Kingdom.
Aurelio
A
Reyes
NIMR-National Institute for Medical Research, Mill Hill, London, United Kingdom.
Ian J
IJ
Holt
NIMR-National Institute for Medical Research, Mill Hill, London, United Kingdom.
Antonella
A
Spinazzola
D000596:Amino Acids / Q000172:deficiency* / Q000378:metabolism; D019069:Cell Respiration; D003600:Cytosol / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis; D063269:Mitochondrial Turnover; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D000596:Amino Acids; D024101:Mitochondrial Proteins; D012333:RNA, Messenger