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Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites

Authors :
Søs Grønbæk Holdgaard
Kenji Maeda
Anders H. Lund
Emiliano Maiani
Vladimir V. Rogov
Franco Locatelli
Matteo Lambrughi
Mads Møller Foged
Letizia Lanzetti
Susana Eibes
Elena Papaleo
Nicole Wesch
Andreas Brech
Simon Bekker-Jensen
Marja Jäättelä
Lisa B. Frankel
Daniela De Zio
Francesca Nazio
Lea M. Harder
Valentina Cianfanelli
Laura R. de la Ballina
Emanuela Pupo
Michal Lubas
Francesco Cecconi
Marin Barisic
Volker Dötsch
Julie C. Nielsen
Jens S. Andersen
Source :
Nature Communications, Vol 10, Iss 1, Pp 1-19 (2019), Holdgaard, S G, Cianfanelli, V, Pupo, E, Lambrughi, M, Lubas, M, Nielsen, J C, Eibes, S, Maiani, E, Harder, L M, Wesch, N, Foged, M M, Maeda, K, Nazio, F, de la Ballina, L R, Dötsch, V, Brech, A, Frankel, L B, Jäättelä, M, Locatelli, F, Barisic, M, Andersen, J S, Bekker-Jensen, S, Lund, A H, Rogov, V V, Papaleo, E, Lanzetti, L, De Zio, D & Cecconi, F 2019, ' Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites ', Nature Communications, vol. 10, 4176, pp. 4176 . https://doi.org/10.1038/s41467-019-12094-9, Holdgaard, S G, Cianfanelli, V, Pupo, E, Lambrughi, M, Lubas, M, Nielsen, J C, Eibes, S, Maiani, E, Harder, L M, Wesch, N, Foged, M M, Maeda, K, Nazio, F, de la Ballina, L R, Dötsch, V, Brech, A, Frankel, L B, Jäättelä, M, Locatelli, F, Barisic, M, Andersen, J S, Bekker-Jensen, S, Lund, A H, Rogov, V V, Papaleo, E, Lanzetti, L, De Zio, D & Cecconi, F 2019, ' Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites ', Nature Communications, vol. 10, no. 1, 4176, pp. 1-19 . https://doi.org/10.1038/s41467-019-12094-9, Nature Communications
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.<br />Centrosomes drive mitotic spindle formation and chromosome segregation. Here, the authors show that centrosome stability is regulated by selective autophagic degradation of centriolar satellite components in a process they term doryphagy, connecting autophagy and chromosomal integrity.

Details

Language :
English
ISSN :
20411723
Database :
OpenAIRE
Journal :
Nature Communications, Vol 10, Iss 1, Pp 1-19 (2019), Holdgaard, S G, Cianfanelli, V, Pupo, E, Lambrughi, M, Lubas, M, Nielsen, J C, Eibes, S, Maiani, E, Harder, L M, Wesch, N, Foged, M M, Maeda, K, Nazio, F, de la Ballina, L R, Dötsch, V, Brech, A, Frankel, L B, Jäättelä, M, Locatelli, F, Barisic, M, Andersen, J S, Bekker-Jensen, S, Lund, A H, Rogov, V V, Papaleo, E, Lanzetti, L, De Zio, D & Cecconi, F 2019, ' Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites ', Nature Communications, vol. 10, 4176, pp. 4176 . https://doi.org/10.1038/s41467-019-12094-9, Holdgaard, S G, Cianfanelli, V, Pupo, E, Lambrughi, M, Lubas, M, Nielsen, J C, Eibes, S, Maiani, E, Harder, L M, Wesch, N, Foged, M M, Maeda, K, Nazio, F, de la Ballina, L R, Dötsch, V, Brech, A, Frankel, L B, Jäättelä, M, Locatelli, F, Barisic, M, Andersen, J S, Bekker-Jensen, S, Lund, A H, Rogov, V V, Papaleo, E, Lanzetti, L, De Zio, D & Cecconi, F 2019, ' Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites ', Nature Communications, vol. 10, no. 1, 4176, pp. 1-19 . https://doi.org/10.1038/s41467-019-12094-9, Nature Communications
Accession number :
edsair.doi.dedup.....d20da61559cd0c0cf8e5f0e33705d0ff
Full Text :
https://doi.org/10.1038/s41467-019-12094-9