Link: Amino Acid Starvation Has Opposite Effects on Mitochondrial and Cytosolic Protein Synthesis (PLoS One)
Proteins form a substantial component of cellular mass, and their synthesis from amino acids is a one of the cell's principal energy expenditures. Amino acids have a second purpose, however - they can be catabolised and used as a a metabolite in the cell's mitochondria. Conversely, they can also be synthesised (at a significant expense of ATP) from precursor molecules, also derived partly from mitochondrial pathways. This puts the mitochondria at an important control point in protein and energy homeostasis, especially in conditions of amino acid scarcity.
In this paper, researchers from the MRC Mitochondrial Biology unit and the NIMR investigated the response of human cells to conditions of amino acid scarcity. They find that when amino acids are scarce, mitochondrial respiration and membrane potential increases, as does mitochondrial protein synthesis, but with no concomitant mitochondrial biogenesis. Cytosolic protein synthesis is downregulated, and cell cycle arrest was observed after 30 hours of amino acid starvation, 24 hours after the increase in mitochondrial protein synthesis.
Paradoxically, components of amino acid catabolic pathways were observed to be upregulated, with a decrease in amino acid anabolism, as measured by increased expression of glycine catabolism proteins and downregulation of asparagine synthetase. The authors suggest that the downregulation of cytosolic proteins is mediated by TORC1 and serves to reduce cell proliferation during amino acid scarcity, rather than as a way of reducing energy consumption. It is also suggested that this evidence shows that mitochondrial components can be replaced, rather than having to synthesise new mitochondria constantly.
Additionally, the findings in this paper indicate the citrate synthase may not be as reliable a measure of mitochondrial mass as previously thought, and that TFAM levels may not always correlate strictly with mtDNA copy number.
Proteins form a substantial component of cellular mass, and their synthesis from amino acids is a one of the cell's principal energy expenditures. Amino acids have a second purpose, however - they can be catabolised and used as a a metabolite in the cell's mitochondria. Conversely, they can also be synthesised (at a significant expense of ATP) from precursor molecules, also derived partly from mitochondrial pathways. This puts the mitochondria at an important control point in protein and energy homeostasis, especially in conditions of amino acid scarcity.
In this paper, researchers from the MRC Mitochondrial Biology unit and the NIMR investigated the response of human cells to conditions of amino acid scarcity. They find that when amino acids are scarce, mitochondrial respiration and membrane potential increases, as does mitochondrial protein synthesis, but with no concomitant mitochondrial biogenesis. Cytosolic protein synthesis is downregulated, and cell cycle arrest was observed after 30 hours of amino acid starvation, 24 hours after the increase in mitochondrial protein synthesis.
Paradoxically, components of amino acid catabolic pathways were observed to be upregulated, with a decrease in amino acid anabolism, as measured by increased expression of glycine catabolism proteins and downregulation of asparagine synthetase. The authors suggest that the downregulation of cytosolic proteins is mediated by TORC1 and serves to reduce cell proliferation during amino acid scarcity, rather than as a way of reducing energy consumption. It is also suggested that this evidence shows that mitochondrial components can be replaced, rather than having to synthesise new mitochondria constantly.
Additionally, the findings in this paper indicate the citrate synthase may not be as reliable a measure of mitochondrial mass as previously thought, and that TFAM levels may not always correlate strictly with mtDNA copy number.
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