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<p>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 <i>Caenorhabditis</i> <i>elegans</i> and <i>Drosophila melanogaster</i>. 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.</p>

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Rpl12 is a conserved ribophagy receptor

  • 期刊论文

  • 发表日期：

    2025年2月11日

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  • Yuting Chen,
  • Jiaxin Hu,
  • Pengwei Zhao,
  • Jie Fang,
  • Yingqi Kuang,
  • Zhaojie Liu,
  • Shuling Dong,
  • Weijing Yao,
  • Yuanyuan Ding,
  • Xinhui Wang,
  • Yibin Pan,
  • Jianbin Wu,
  • Jingwei Zhao,
  • Jing Yang,
  • Zhenzhong Xu,
  • Xiaodi Liu,
  • Yi Zhang,
  • Choufei Wu,
  • Liqin Zhang,
  • Mingzhu Fan,
  • Shan Feng,
  • Zhi Hong,
  • Zhangming Yan,
  • Hongguang Xia,
  • Kaiyue Tang,
  • Bing Yang,
  • Wei Liu,
  • Qiming Sun,
  • Kunrong Mei,
  • Wei Zou,
  • Yunpeng Huang,
  • Du Feng,
  • Cong Yi

摘要

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.