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Midbody ring disposal by autophagy is a post-abscission event of cytokinesis

Abstract

At the end of cytokinesis, the dividing cells are connected by an intercellular bridge, containing the midbody along with a single, densely ubiquitylated, circular structure called the midbody ring (MR)1,2,3. Recent studies revealed that the MR serves as a target site for membrane delivery and as a physical barrier between the prospective daughter cells2,3. The MR materializes in telophase, localizes to the intercellular bridge during cytokinesis, and moves asymmetrically into one cell after abscission2,3. Daughter cells rarely accumulate MRs of previous divisions2,3, but how these large structures finally disappear remains unknown. Here, we show that MRs are discarded by autophagy, which involves their sequestration into autophagosomes and delivery to lysosomes for degradation. Notably, autophagy factors, such as the ubiquitin adaptor p62 (Refs 4, 5) and the ubiquitin-related protein Atg8 (ref. 6), associate with the MR during abscission, suggesting that autophagy is coupled to cytokinesis. Moreover, MRs accumulate in cells of patients with lysosomal storage disorders, indicating that defective MR disposal is characteristic of these diseases. Thus our findings suggest that autophagy has a broader role than previously assumed, and that cell renovation by clearing from superfluous large macromolecular assemblies, such as MRs, is an important autophagic function.

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Figure 1: The ubiquitin adaptor protein p62 acts as an auxiliary factor in MR disposal.
Figure 2: MRs are engulfed by autophagosomes and lysosomes.
Figure 3: MRs accumulate in cells compromised in autophagy.
Figure 4: MR accumulation as a function of the growth rate.
Figure 5: MR accumulations in human lysosomal storage disorders.

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Acknowledgements

We thank Masaaki Komatsu and Keiji Tanaka for providing Atg7 knockout MEFs and controls, the Bryan Tsou laboratory and Tim Ammon for technical support and help, and Alex Buchberger for comments on the manuscript. S.J. is supported by the Max Planck Society, Center for Integrated Protein Science Munich, and RUBICON EU Network of Excellence.

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C.P. conducted the experiments and S.J. wrote the manuscript. Both authors conceived the experiments and discussed the results.

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Correspondence to Stefan Jentsch.

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The authors declare no competing financial interests.

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Pohl, C., Jentsch, S. Midbody ring disposal by autophagy is a post-abscission event of cytokinesis. Nat Cell Biol 11, 65–70 (2009). https://doi.org/10.1038/ncb1813

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