Abstract
Selective autophagy of the nucleus, known as nucleophagy, targets nuclear components for degradation. The molecular mechanisms underlying nucleophagy remain inadequately understood. In this study, we identify a nucleophagy receptor, Npr1, in the fission yeast Schizosaccharomyces pombe. Npr1 is an Atg8-binding multi-transmembrane protein localized to the outer nuclear membrane. It functions redundantly with another autophagy receptor, Epr1, to promote nitrogen starvation-induced nucleophagy. In the absence of both Npr1 and Epr1, starved cells exhibit abnormal nuclear morphology and reduced survival. During nucleophagy, the nuclear envelope (NE) forms outward protrusions where Atg8 co-localizes with Npr1 and/or Epr1. These protrusions subsequently detach from the NE, resulting in the formation of autophagosomes that contain nucleophagy cargo. Notably, artificially enhancing chromatin association with the inner nuclear membrane leads to NE protrusions that fail to detach, thereby aborting nucleophagy. Our findings provide mechanistic insights into nucleophagy and suggest that abortive nucleophagy protects chromatin from degradation.
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Acknowledgements
We are grateful to Ying Liu and He-Xia Luo of the NIBS EM Facility for their assistance with EM analysis. We also thank Wen-Yi Huang, Yin-Hua Lin, and Ke Du of Guangzhou Computational Super-Resolution Biotech Co., Ltd. for their support in live-cell imaging with their super-resolution microscope (HIS-SIM). Additionally, we thank Yi-Feng Jiang, Zhen-Hua Zhang, and Hao Zhang of the ZEISS Microscopy Customer Center in Beijing, as well as Eric Ho of Dragonfly, for their help with FIB-SEM analysis. We extend our gratitude to Meng-Li Shi for her assistance in drawing the models shown in Fig. 7g. This work was supported by the National Key R&D Program of China (2024YFA0917400 to L.-L.D.) and other grants from the Ministry of Science and Technology of China, the Beijing municipal government, and Tsinghua University to M.-Q.D. and L.-L.D.
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Conceptualization: Z.-H.M. and L.-L.D. Methodology and investigation: Z.-H.M., Z.-Q.P., Z.-D.J., G.-C.S., Y.H., F.S., C.-X.Z., Y.-F.J., M.-Q.D., and L.-L.D. Writing—original draft: Z.-H.M. and L.-L.D. Writing—review and editing: Z.-H.M. and L.-L.D. Funding acquisition: M.-Q.D. and L.-L.D.
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Ma, ZH., Pan, ZQ., Jiang, ZD. et al. Nucleophagy is promoted by two autophagy receptors and inhibited by chromatin-nuclear envelope tethering in fission yeast. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71237-x
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DOI: https://doi.org/10.1038/s41467-026-71237-x
