Dot1 triggers a conserved ribophagy signal to govern ribosome quality and longevity by methylating Rpl12.

Dot1/DOT1L methylates Rpl12 to create a conserved ribophagy “eat-me” signal, with starvation-linked methylation at K41 and K48 in Saccharomyces cerevisiae.

• Why it matters: Ribophagy depends on ribosome-specific recognition, but the molecular “eat-me” marks that direct autophagic targeting were unclear.
• What they did: In Saccharomyces cerevisiae, nutrient deprivation triggers Dot1-dependent Rpl12 methylation at K41 and K48, boosting Atg11 interaction and initiating ribophagy via the TOR-Atg1-Rpl12 axis. In mammals and Drosophila melanogaster, starvation or Dot1 homolog activity promotes DOT1L/RpL12 or Gpp-methylated RpL12 colocalization with autophagy markers.
• The result: Methylation-deficient RpL12 mutants in Drosophila melanogaster show impaired ribophagy and developmental defects, accelerated aging, muscle degeneration, and reduced stress resistance, linking the conserved signal to ribosome quality and longevity.

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