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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Eggert, U. S., Mitchison, T. J. & Field, C. M. Animal cytokinesis: from parts list to mechanisms. Annu. Rev. Biochem. 75, 543–566 (2006).
Gromley, A. et al. Centriolin anchoring of exocyst and SNARE complexes at the midbody is required for secretory-vesicle-mediated abscission. Cell 123, 75–87 (2005).
Pohl, C. & Jentsch, S. Final stages of cytokinesis and midbody ring formation are controlled by BRUCE. Cell 132, 832–845 (2008).
Pankiv, S. et al. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J. Biol. Chem. 282, 24131–24145 (2007).
Ding, W. X. & Yin, X. M. Sorting, recognition and activation of the misfolded protein degradation pathways through macroautophagy and the proteasome. Autophagy 4, 141–150 (2008).
Ichimura, Y. et al. A ubiquitin-like system mediates protein lipidation. Nature 408, 488–492 (2000).
Mishima, M., Kaitna, S. & Glotzer, M. Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity. Dev. Cell 2, 41–54 (2002).
Mukai, A. et al. Dynamic regulation of ubiquitylation and deubiquitylation at the central spindle during cytokinesis. J. Cell Sci. 121, 1325–1333 (2008).
Bartke, T., Pohl, C., Pyrowolakis, G. & Jentsch, S. Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase. Mol. Cell 14, 801–811 (2004).
Klionsky, D. J. & Ohsumi, Y. Vacuolar import of proteins and organelles from the cytoplasm. Annu. Rev. Cell Dev Biol. 15, 1–32. (1999).
Jager, S. et al. Role for Rab7 in maturation of late autophagic vacuoles. J. Cell Sci. 117, 4837–4848 (2004).
Seglen, P. O. & Gordon, P. B. 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc. Natl Acad. Sci. USA 79, 1889–1892 (1982).
Hoyer-Hansen, M. et al. Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-β, and Bcl-2. Mol. Cell 25, 193–205 (2007).
Pattingre, S. et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122, 927–39 (2005).
Liang, X. H. et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402, 672–676 (1999).
Gonzalez-Polo, R. A. et al. The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death. J. Cell Sci. 118, 3091–3102 (2005).
Jeyakumar, M., Dwek, R. A., Butters, T. D. & Platt, F. M. Storage solutions: treating lysosomal disorders of the brain. Nature Rev. Neurosci. 6, 713–725 (2005).
Mach, L. Biosynthesis of lysosomal proteinases in health and disease. Biol. Chem. 383, 751–756 (2002).
Hein, L. K. et al. α-L-iduronidase premature stop codons and potential read-through in mucopolysaccharidosis type I patients. J. Mol. Biol. 338, 453–462 (2004).
Settembre, C. et al. A block of autophagy in lysosomal storage disorders. Hum. Mol. Genet. 17, 119–129 (2008).
Kiselyov, K., Jennigs, J. J., Jr., Rbaibi, Y. & Chu, C. T. Autophagy, mitochondria and cell death in lysosomal storage diseases. Autophagy 3, 259–262 (2007).
Scherz-Shouval, R. & Elazar, Z. ROS, mitochondria and the regulation of autophagy. Trends Cell Biol. 17, 422–427 (2007).
Karantza-Wadsworth, V. et al. Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev. 21, 1621–1635 (2007).
Mathew, R. et al. Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev. 21, 1367–1381 (2007).
Levine, B. & Klionsky, D. J. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 6, 463–477 (2004).
Eskelinen, E. L. et al. Inhibition of autophagy in mitotic animal cells. Traffic 3, 878–893 (2002).
Tasdemir, E. et al. Cell cycle-dependent induction of autophagy, mitophagy and reticulophagy. Cell Cycle 6, 2263–2267 (2007).
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.
Author information
Authors and Affiliations
Contributions
C.P. conducted the experiments and S.J. wrote the manuscript. Both authors conceived the experiments and discussed the results.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Information
Supplementary Information (PDF 914 kb)
Supplementary Information
Supplementary Movie 1 (MOV 5227 kb)
Supplementary Information
Supplementary movie 2 (MOV 9985 kb)
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ncb1813
This article is cited by
-
Secreted midbody remnants are a class of extracellular vesicles molecularly distinct from exosomes and microparticles
Communications Biology (2021)
-
Membrane and organelle dynamics during cell division
Nature Reviews Molecular Cell Biology (2020)
-
The post-abscission midbody is an intracellular signaling organelle that regulates cell proliferation
Nature Communications (2019)
-
ULK1 affects cell viability of goat Sertoli cell by modulating both autophagy and apoptosis
In Vitro Cellular & Developmental Biology - Animal (2019)
-
Routes and machinery of primary cilium biogenesis
Cellular and Molecular Life Sciences (2017)