Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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.
I: Nature Communications, Bind 10, Nr. 1, 4176, 2019, s. 1-19.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites
AU - Holdgaard, Søs Grønbæk
AU - Cianfanelli, Valentina
AU - Pupo, Emanuela
AU - Lambrughi, Matteo
AU - Lubas, Michal
AU - Nielsen, Julie C
AU - Eibes, Susana
AU - Maiani, Emiliano
AU - Harder, Lea M
AU - Wesch, Nicole
AU - Foged, Mads Møller
AU - Maeda, Kenji
AU - Nazio, Francesca
AU - de la Ballina, Laura R
AU - Dötsch, Volker
AU - Brech, Andreas
AU - Frankel, Lisa B
AU - Jäättelä, Marja
AU - Locatelli, Franco
AU - Barisic, Marin
AU - Andersen, Jens S
AU - Bekker-Jensen, Simon
AU - Lund, Anders H
AU - Rogov, Vladimir V
AU - Papaleo, Elena
AU - Lanzetti, Letizia
AU - De Zio, Daniela
AU - Cecconi, Francesco
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-019-12094-9
DO - 10.1038/s41467-019-12094-9
M3 - Journal article
C2 - 31519908
VL - 10
SP - 1
EP - 19
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 4176
ER -
ID: 227299229