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

Søs Grønbæk Holdgaard, Valentina Cianfanelli, Emanuela Pupo, Matteo Lambrughi, Michal Lubas, Julie C. Nielsen, Susana Eibes, Emiliano Maiani, Lea M. Harder, Nicole Wesch, Mads Møller Foged, Kenji Maeda, Francesca Nazio, Laura R. de la Ballina, Volker Dötsch, Andreas Brech, Lisa B. Frankel, Marja Jäättelä, Franco Locatelli, Marin Barisic, Jens S. Andersen, Simon Bekker-Jensen, Anders H. Lund, Vladimir V. Rogov, Elena Papaleo, Letizia Lanzetti, Daniela De Zio and Francesco Cecconi ()
Additional contact information
Søs Grønbæk Holdgaard: Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center
Valentina Cianfanelli: Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center
Emanuela Pupo: University of Torino Medical School
Matteo Lambrughi: Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center
Michal Lubas: University of Copenhagen
Julie C. Nielsen: University of Copenhagen
Susana Eibes: Cell Division Laboratory, Danish Cancer Society Research Center
Emiliano Maiani: Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center
Lea M. Harder: University of Southern Denmark
Nicole Wesch: Goethe University Frankfurt
Mads Møller Foged: Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center
Kenji Maeda: Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center
Francesca Nazio: IRCCS Bambino Gesù Children’s Hospital
Laura R. de la Ballina: University of Oslo
Volker Dötsch: Goethe University Frankfurt
Andreas Brech: Oslo University Hospital
Lisa B. Frankel: University of Copenhagen
Marja Jäättelä: Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center
Franco Locatelli: IRCCS Bambino Gesù Children’s Hospital
Marin Barisic: Cell Division Laboratory, Danish Cancer Society Research Center
Jens S. Andersen: University of Southern Denmark
Simon Bekker-Jensen: University of Copenhagen
Anders H. Lund: University of Copenhagen
Vladimir V. Rogov: Goethe University Frankfurt
Elena Papaleo: Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center
Letizia Lanzetti: University of Torino Medical School
Daniela De Zio: Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center
Francesco Cecconi: Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center

Nature Communications, 2019, vol. 10, issue 1, 1-19

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12094-9

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