Cell starvation through proteasome block
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Proteasome inhibition is lethal, and there is strong interest in the underlying mechanisms of this. In addition to degrading proteins, the proteasome has a role in amino acid recycling, so
Suraweera et al. asked whether this might cause lethality following proteasome inhibition. In yeast, mammalian cells and Drosophila melanogaster, amino acid supplementation following
proteasome inhibition rescued viability; however, it did not rescue proteasome function, indicating that amino acid starvation is the underlying cause of lethality. Moreover, amino acid
scarcity resulting from proteasome inhibition signals the induction of autophagy, which attempts to replenish the amino acid pool and to restore homeostasis. The authors propose that
lethality following proteasome inhibition may be due to the accumulation of proteasome substrates and the sequestration of amino acids that would otherwise be recycled.
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