Protein Synthesis upon Acute Nutrient Restriction Relies on Proteasome Function

Science, 310, 1960-1963, 2005

Speaker : 張儀君                             Date : 2006’ 02’ 22 14:10~15:00

Commentator : 徐麗君 老師                    Place : Room 601

Abstract

In mammalian cells, protein synthesis relies on the continuous uptake of essential amino acid from the environment. Acute amino acid restriction may occur several physiological and pathophysiological conditions. The mechanisms that protect cells against amino acid deprivation are partially understood. Recent studies indicate the production of amino acids by autophagic degradation of ‘self ’ proteins may allow for the maintenance of energy homeostasis. The autophagosomal-lysosomal system requires hours to become effective. Mammalian cells contain multiple proteolytic systems to carry out protein degradation. Nonlysosomal degradation by means of the proteasomal system is known to be induced during long-term fasting. The role of the proteasome in maintaining the intracellular amino acid pool during acute nutrient deprivation has remained unexplored. In this report, the authors provide evidence for a critical role of the proteasome in supplying amino acids for sustained protein synthesis upon amino acid restriction, and the lysosomal system unable to maintain a sufficient intracellular amino acid pool. Amino acids for the synthesis of new proteins were supplied by the degradation of preexisting proteins, but most of the newly synthesized proteins were protected against immediate degradation after translation, both under normal conditions and upon amino acid restriction. Thus, the proteasome plays a crucial role in cell survival after acute disruption of amino acid supply. The proteasome has been shown to degrade polypeptide during synthesis, if they carry specialized N-terminal degradation signal, but this mechanism would be preferentially used in cell regulation rather than during routine housekeeping process.

References

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