Ribosomes (white) end up in the vacuole in starving cells, unless either of the ribophagy proteins Ubp3p (middle) or Bre5p (bottom) is missing.


Starving cells seem to first gobble up their ribosomes before they start cannibalizing anything and everything, based on results from Claudine Kraft, Matthias Peter, and colleagues (ETH, Zürich, Switzerland). Using a ribosome-specific autophagy pathway, cells might match ribosome number to metabolic needs.

When nutrients are scarce, autophagy allows cells to degrade their internal components and focus on only the essentials. Kraft et al. noticed that one of the first sets of components dumped into vacuoles, where autophagocytosed products are digested, included ribosomes. Their early deposition required several known autophagy genes.

Autophagosomes can engulf either bulk cytoplasm, and anything that comes along with it, or only specific elements, such as mitochondria. According to the new results, ribosomes were taken in selectively by a pathway that the authors dubbed ribophagy, which depended on a ubiquitin-cleaving enzyme called Ubp3p and its cofactor, Bre5p.

Ubp3p mutant cells die upon nutrient starvation, possibly because of their inability to digest ribosomes—an excellent first option for autophagy, according to Peter. “They're rich in protein and RNA, so they provide plenty of building blocks like amino acids. Maybe the starvation response isn't all-or-none. Cells could first get rid of ribosomes and only as a last resort randomly degrade cytoplasm, which can be damaging. You never know what might get destroyed that you might need later.”

Peter also imagines that ribophagy is not restricted to starving cells. “Half of a cell's energy goes into ribosome biogenesis and protein synthesis,” he says. Autophagy of these very stable organelles might “make sure a cell has only as many as it needs to translate its proteins. Perhaps ribosome number may be adjusted all the time to growth conditions.” The pathway might also destroy faulty ribosomes. So far, however, how the organelles are marked as defective or surplus is not known.

Kraft, C., et al.
Nat. Cell Biol.