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Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites.
Holdgaard, Søs Grønbæk; Cianfanelli, Valentina; Pupo, Emanuela; Lambrughi, Matteo; Lubas, Michal; Nielsen, Julie C; Eibes, Susana; Maiani, Emiliano; Harder, Lea M; Wesch, Nicole; Foged, Mads Møller; Maeda, Kenji; Nazio, Francesca; de la Ballina, Laura R; Dötsch, Volker; Brech, Andreas; Frankel, Lisa B; Jäättelä, Marja; Locatelli, Franco; Barisic, Marin; Andersen, Jens S; Bekker-Jensen, Simon; Lund, Anders H; Rogov, Vladimir V; Papaleo, Elena; Lanzetti, Letizia; De Zio, Daniela; Cecconi, Francesco.
Afiliación
  • Holdgaard SG; Cell Stress and Survival Unit, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center, Copenhagen, 2100, Denmark.
  • Cianfanelli V; Cell Stress and Survival Unit, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center, Copenhagen, 2100, Denmark.
  • Pupo E; Department of Oncology, University of Torino Medical School, Turin, 10100, Italy.
  • Lambrughi M; Candiolo Cancer Institute, FPO - IRCCS, Candiolo, 10060, Italy.
  • Lubas M; Computational Biology Laboratory, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center, Copenhagen, 2100, Denmark.
  • Nielsen JC; Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, 2200, Denmark.
  • Eibes S; Center for Healthy Aging, University of Copenhagen, Copenhagen, 2200, Denmark.
  • Maiani E; Cell Division Laboratory, Danish Cancer Society Research Center, Copenhagen, 2100, Denmark.
  • Harder LM; Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, 2200, Denmark.
  • Wesch N; Cell Stress and Survival Unit, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center, Copenhagen, 2100, Denmark.
  • Foged MM; Computational Biology Laboratory, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center, Copenhagen, 2100, Denmark.
  • Maeda K; Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, 5230, Denmark.
  • Nazio F; Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University Frankfurt, 60438, Frankfurt, Germany.
  • de la Ballina LR; Cell Death and Metabolism Unit, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center, Copenhagen, 2100, Denmark.
  • Dötsch V; Cell Death and Metabolism Unit, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center, Copenhagen, 2100, Denmark.
  • Brech A; Department of Pediatric Hemato-Oncology and Cell and Gene therapy, IRCCS Bambino Gesù Children's Hospital, Rome, 00143, Italy.
  • Frankel LB; Department of Molecular Medicine, Institute of Basic Medical Sciences and Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0317, Oslo, Norway.
  • Jäättelä M; Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University Frankfurt, 60438, Frankfurt, Germany.
  • Locatelli F; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, 0379, Oslo, Norway.
  • Barisic M; Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0379, Oslo, Norway.
  • Andersen JS; Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, 2200, Denmark.
  • Bekker-Jensen S; RNA and Autophagy group, Danish Cancer Society Research Center, Copenhagen, 2100, Denmark.
  • Lund AH; Cell Death and Metabolism Unit, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center, Copenhagen, 2100, Denmark.
  • Rogov VV; Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.
  • Papaleo E; Department of Pediatric Hemato-Oncology and Cell and Gene therapy, IRCCS Bambino Gesù Children's Hospital, Rome, 00143, Italy.
  • Lanzetti L; Department of Gynecology/Obstetrics and Pediatrics, Sapienza University of Rome, Rome, 00185, Italy.
  • De Zio D; Cell Division Laboratory, Danish Cancer Society Research Center, Copenhagen, 2100, Denmark.
  • Cecconi F; Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, 2200, Denmark.
Nat Commun ; 10(1): 4176, 2019 09 13.
Article en En | MEDLINE | ID: mdl-31519908
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Centriolos / Centrosoma / Mitosis Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2019 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Centriolos / Centrosoma / Mitosis Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2019 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido