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Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites.
- Source :
-
Nature communications [Nat Commun] 2019 Sep 13; Vol. 10 (1), pp. 4176. Date of Electronic Publication: 2019 Sep 13. - Publication Year :
- 2019
-
Abstract
- The centrosome is the master orchestrator of mitotic spindle formation and chromosome segregation in animal cells. Centrosome abnormalities are frequently observed in cancer, but little is known of their origin and about pathways affecting centrosome homeostasis. Here we show that autophagy preserves centrosome organization and stability through selective turnover of centriolar satellite components, a process we termed doryphagy. Autophagy targets the satellite organizer PCM1 by interacting with GABARAPs via a C-terminal LIR motif. Accordingly, autophagy deficiency results in accumulation of large abnormal centriolar satellites and a resultant dysregulation of centrosome composition. These alterations have critical impact on centrosome stability and lead to mitotic centrosome fragmentation and unbalanced chromosome segregation. Our findings identify doryphagy as an important centrosome-regulating pathway and bring mechanistic insights to the link between autophagy dysfunction and chromosomal instability. In addition, we highlight the vital role of centriolar satellites in maintaining centrosome integrity.
- Subjects :
- Autophagy genetics
Cell Cycle genetics
Cell Cycle physiology
Cell Line, Tumor
Chromatography, Liquid
Humans
Immunoblotting
Magnetic Resonance Spectroscopy
Mass Spectrometry
Microscopy, Fluorescence
Microtubules metabolism
Mitosis genetics
Molecular Dynamics Simulation
Autophagy physiology
Centrioles metabolism
Centrosome metabolism
Mitosis physiology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 31519908
- Full Text :
- https://doi.org/10.1038/s41467-019-12094-9