Chen, Y., Hu, J., Zhao, P., Fang, J., Kuang, Y., Liu, Z., Dong, S., Yao, W., Ding, Y., Wang, X., Pan, Y., Wu, J., Zhao, J., Yang, J., Xu, Z., Liu, X., Zhang, Y., Wu, C., Zhang, L., Fan, M., Feng, S., Hong, Z., Yan, Z., Xia, H., Tang, K., Yang, B., Liu, W., Sun, Q., Mei, K., Zou, W., Huang, Y., Feng, D., Yi, C. (2025). Rpl12 is a conserved ribophagy receptor.  Nat. Cell Biol. 27(3): 477--492.

FBrf0261900

Research paper

Ribophagy is a selective autophagic process that regulates ribosome turnover. Although NUFIP1 has been identified as a mammalian receptor for ribophagy, its homologues do not exist in yeast and nematodes. Here we demonstrate that Rpl12, a ribosomal large subunit protein, functions as a conserved ribophagy receptor in multiple organisms. Disruption of Rpl12-Atg8s binding leads to significant accumulation of ribosomal proteins and rRNA, while Atg1-mediated Rpl12 phosphorylation enhances its association with Atg11, thus triggering ribophagy during starvation. Ribophagy deficiency accelerates cell death induced by starvation and pathogen infection, leading to impaired growth and development and a shortened lifespan in both Caenorhabditis elegans and Drosophila melanogaster. Moreover, ribophagy deficiency results in motor impairments associated with ageing, while the overexpression of RPL12 significantly improves movement defects induced by starvation, ageing and Aβ accumulation in fly models. Our findings suggest that Rpl12 functions as a conserved ribophagy receptor vital for ribosome metabolism and cellular homeostasis.