Cell Biology

Recycle to Survive

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Science  28 Sep 2012:
Vol. 337, Issue 6102, pp. 1584
DOI: 10.1126/science.337.6102.1584-b

The proteasome is essential for the controlled degradation of proteins in all cells. Although it is well established that proteasome inhibition is lethal, the underlying mechanism is less clear. Working in yeast, mammalian cells, and flies, Suraweera et al. found that proteasome inhibition caused a critical shortage of amino acids, leading to cell death. Cells could cope with high levels of undegraded proteasome substrates, but not with the resulting depletion of key amino acids. The lethality of proteasome inhibition was rescued upon amino acid supplementation. Furthermore, the shortage of select amino acids induced autophagy when the proteasome was inhibited, linking proteasome impairment and autophagy induction. Thus, the proteasome serves a basic housekeeping function as a recycling machine, beyond a simple waste disposal system, and it is the lack of critical amino acids that kills cells when the proteasome is compromised, not the accumulation of protein waste.

Mol. Cell 47, 10.1016/j.molcel.2012.08.003 (2012).

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