Rpl12 is a conserved ribophagy receptor

Yuting Chen^#^{1

2}, Jiaxin Hu^#³, Pengwei Zhao^#¹, Jie Fang^#^{4

5

6}, Yingqi Kuang¹, Zhaojie Liu^{2

7}, Shuling Dong^{1

8}, Weijing Yao¹, Yuanyuan Ding⁹, Xinhui Wang¹⁰, Yibin Pan^{11

12}, Jianbin Wu¹³, Jingwei Zhao¹³, Jing Yang¹⁴, Zhenzhong Xu^{14

15}, Xiaodi Liu², Yi Zhang¹, Choufei Wu⁸, Liqin Zhang⁸, Mingzhu Fan¹⁶, Shan Feng¹⁶, Zhi Hong^{17

18}, Zhangming Yan¹⁹, Hongguang Xia¹, Kaiyue Tang²⁰, Bing Yang²⁰, Wei Liu¹, Qiming Sun¹, Kunrong Mei²¹, Wei Zou^{22

23}, Yunpeng Huang²⁴, Du Feng^{25

26}, Cong Yi²⁷

Affiliations

¹ Department of Biochemistry and Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² State Key Laboratory of Respiratory Disease, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
³ Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
⁴ The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China.
⁵ Institute of Translational Medicine, Zhejiang University, Hangzhou, China.
⁶ Department of Cell Biology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁷ Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
⁸ Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Life Sciences, Huzhou University, Huzhou, China.
⁹ School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.
¹⁰ School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.
¹¹ Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
¹² Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
¹³ Department of Pathology of Sir Run Run Shaw Hospital, and Department of Human Anatomy, Histology and Embryology, System Medicine Research Center, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
¹⁴ Department of Neurobiology and Department of Anesthesiology of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
¹⁵ NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China.
¹⁶ Mass Spectrometry and Metabolomics Core Facility, Key Laboratory of Structural Biology of Zhejiang Province, Westlake University, Hangzhou, China.
¹⁷ Department of Neurology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
¹⁸ Centre for Cellular Biology and Signaling, Zhejiang University-University of Edinburgh Institute, Haining, China.
¹⁹ School of Life Sciences, Tsinghua University, Beijing, China.
²⁰ Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.
²¹ School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China. kmei@tju.edu.cn.
²² The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China. zouwei@zju.edu.cn.
²³ Institute of Translational Medicine, Zhejiang University, Hangzhou, China. zouwei@zju.edu.cn.
²⁴ Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China. huangyp@ucas.ac.cn.
²⁵ State Key Laboratory of Respiratory Disease, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China. Fenglab@gzhmu.edu.cn.
²⁶ Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. Fenglab@gzhmu.edu.cn.
²⁷ Department of Biochemistry and Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. yiconglab@zju.edu.cn.

^# Contributed equally.

PMID: 39934334
DOI: 10.1038/s41556-024-01598-2

Rpl12 is a conserved ribophagy receptor

Yuting Chen et al. Nat Cell Biol. 2025 Mar.

. 2025 Mar;27(3):477-492.

doi: 10.1038/s41556-024-01598-2. Epub 2025 Feb 11.

Authors

Affiliations

¹ Department of Biochemistry and Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² State Key Laboratory of Respiratory Disease, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
³ Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
⁴ The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China.
⁵ Institute of Translational Medicine, Zhejiang University, Hangzhou, China.
⁶ Department of Cell Biology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁷ Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
⁸ Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Life Sciences, Huzhou University, Huzhou, China.
⁹ School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.
¹⁰ School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.
¹¹ Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
¹² Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
¹³ Department of Pathology of Sir Run Run Shaw Hospital, and Department of Human Anatomy, Histology and Embryology, System Medicine Research Center, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
¹⁴ Department of Neurobiology and Department of Anesthesiology of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
¹⁵ NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China.
¹⁶ Mass Spectrometry and Metabolomics Core Facility, Key Laboratory of Structural Biology of Zhejiang Province, Westlake University, Hangzhou, China.
¹⁷ Department of Neurology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
¹⁸ Centre for Cellular Biology and Signaling, Zhejiang University-University of Edinburgh Institute, Haining, China.
¹⁹ School of Life Sciences, Tsinghua University, Beijing, China.
²⁰ Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.
²¹ School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China. kmei@tju.edu.cn.
²² The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China. zouwei@zju.edu.cn.
²³ Institute of Translational Medicine, Zhejiang University, Hangzhou, China. zouwei@zju.edu.cn.
²⁴ Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China. huangyp@ucas.ac.cn.
²⁵ State Key Laboratory of Respiratory Disease, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China. Fenglab@gzhmu.edu.cn.
²⁶ Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. Fenglab@gzhmu.edu.cn.
²⁷ Department of Biochemistry and Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. yiconglab@zju.edu.cn.

^# Contributed equally.

PMID: 39934334
DOI: 10.1038/s41556-024-01598-2

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.

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare no competing interests.

References

1. Panse, V. G. & Johnson, A. W. Maturation of eukaryotic ribosomes: acquisition of functionality. Trends Biochem. Sci. 35, 260–266 (2010). - PubMed - PMC
1. López, A. R. et al. Autophagy-mediated control of ribosome homeostasis in oncogene-induced senescence. Cell Rep. 42, 113381 (2023). - PubMed
1. Kazibwe, Z., Liu, A. Y., MacIntosh, G. C. & Bassham, D. C. The ins and outs of autophagic ribosome turnover. Cells 8, 1603 (2019). - PubMed - PMC
1. Kraft, C., Deplazes, A., Sohrmann, M. & Peter, M. Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease. Nat. Cell Biol. 10, 602–610 (2008). - PubMed
1. Wyant, G. A. et al. NUFIP1 is a ribosome receptor for starvation-induced ribophagy. Science 360, 751–758 (2018). - PubMed - PMC

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
- Nature Publishing Group
Molecular Biology Databases
- FlyBase
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Rpl12 is a conserved ribophagy receptor

Affiliations

Rpl12 is a conserved ribophagy receptor

Authors

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Molecular Biology Databases

Miscellaneous