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Inhibitors of cytoplasmic protein synthesis purified from rat liver mitochondria


Purified mitochondria from rat liver were found to contain protein synthesis inhibitors, that could be extracted by disruption of mitochondrial membranes and fractionated by gel filtration into two fractions of low and high molecular weight. Small size inhibitors were also released from the latter peak by high ionic strength followed by gel filtration. Both types of factors inhibit incorporation of radioactive amino acids into protein by liver cytoplasmic polysomes programmed with endogenous mRNA or poly U, and by rabbit reticulocyte lysates programmed with added globin mRNA and by incubations of Walker carcinoma cells. They decrease to the same level the cytoplasmic synthesis of proteins for the mitochondrial and extra-mitochondrial compartments in intact cells, but do not appear to inhibit substantially endogenous mitochondrial protein synthesis. Inhibitors were purified by paper chromatography and reverse phase high performance liquid chromatography into fractions which block with the same kinetics the incorporation of [14]leucine and [35]methionine into protein in systems able to initiate protein synthesis, such as reticulocyte lysates or intact cells, but differ in this respect in incubations of liver ribosomes where re-binding of mRNA is a limiting step. Some of these factors behave as oligopeptides that are assumed to inhibit in vitro primarily the initiation stage but whose function in vivo is still undetermined.

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Correspondence to Nestor González-Cadavid.

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Pérez, J.L., Dorta, B. & González-Cadavid, N. Inhibitors of cytoplasmic protein synthesis purified from rat liver mitochondria. Mol Cell Biochem 62, 121–132 (1984).

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  • High Performance Liquid Chromatography
  • Liver Mitochondrion
  • High Ionic Strength
  • Oligopeptides
  • Protein Synthesis Inhibitor