Rpl12是一种保守的核糖噬受体，这一成果由浙江大学医学院易聪团队经过不懈努力而取得。这一研究成果于2025年2月11日发表在国际顶尖学术期刊《自然—细胞生物学》上。

在这里，研究组证明了Rpl12，一种核糖体大亚基蛋白，在多种生物中作为一种保守的核糖体自噬受体起作用。Rpl12 - Atg8s结合的破坏导致核糖体蛋白和rRNA的显著积累，而Atg1介导的Rpl12磷酸化增强了其与Atg11的关联，从而在饥饿期间触发核糖体自噬。核噬缺陷加速饥饿和病原体感染引起的细胞死亡，导致秀丽隐杆线虫和黑腹果蝇生长发育受损和寿命缩短。

此外，核噬缺陷导致与衰老相关的运动障碍，而RPL12过表达可显著改善果蝇模型中由饥饿、衰老和Aβ积累引起的运动缺陷。他们的研究结果表明，Rpl12作为一种保守的核糖体自噬受体，对核糖体代谢和细胞稳态至关重要。

据悉，核糖体自噬是一种调节核糖体周转的选择性自噬过程。虽然NUFIP1已被确定为哺乳动物的核糖噬受体，但其同源物在酵母和线虫中并不存在。

附：英文原文

Title: Rpl12 is a conserved ribophagy receptor

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

Issue&Volume: 2025-02-11

Abstract: 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.

DOI: 10.1038/s41556-024-01598-2

Source: https://www.nature.com/articles/s41556-024-01598-2