Midbody ring disposal by autophagy is a post-abscission event of cytokinesis.
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). Recent studies revealed that the MR serves as a target site for membrane delivery and as a physical barrier between the prospective daughter cells. The MR materializes in telophase, localizes to the intercellular bridge during cytokinesis, and moves asymmetrically into one cell after abscission. Daughter cells rarely accumulate MRs of previous divisions, 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.
Pohl
Christian
C
Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Jentsch
Stefan
S
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002460:Cell Line; D022081:Cell Surface Extensions / Q000378:metabolism* / Q000648:ultrastructure; D048749:Cytokinesis / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D046911:Macromolecular Substances / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins; D015388:Organelles / Q000378:metabolism / Q000648:ultrastructure; D010588:Phagosomes / Q000378:metabolism / Q000648:ultrastructure; D000071456:Sequestosome-1 Protein; D014452:Ubiquitins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C480859:Gabarapl1 protein, mouse; D046911:Macromolecular Substances; D008869:Microtubule-Associated Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D014452:Ubiquitins