A PKD-MFF signaling axis couples mitochondrial fission to mitotic progression.
Fiche publication
Date publication
mai 2021
Journal
Cell reports
Auteurs
Membres identifiés du Cancéropôle Est :
Pr RICCI Roméo, Dr SUMARA Izabela, Dr COMPE Emmanuel, Dr PANGOU Evanthia
Tous les auteurs :
Pangou E, Bielska O, Guerber L, Schmucker S, Agote-Arán A, Ye T, Liao Y, Puig-Gamez M, Grandgirard E, Kleiss C, Liu Y, Compe E, Zhang Z, Aebersold R, Ricci R, Sumara I
Lien Pubmed
Résumé
Mitochondria are highly dynamic organelles subjected to fission and fusion events. During mitosis, mitochondrial fission ensures equal distribution of mitochondria to daughter cells. If and how this process can actively drive mitotic progression remains largely unknown. Here, we discover a pathway linking mitochondrial fission to mitotic progression in mammalian cells. The mitochondrial fission factor (MFF), the main mitochondrial receptor for the Dynamin-related protein 1 (DRP1), is directly phosphorylated by Protein Kinase D (PKD) specifically during mitosis. PKD-dependent MFF phosphorylation is required and sufficient for mitochondrial fission in mitotic but not in interphasic cells. Phosphorylation of MFF is crucial for chromosome segregation and promotes cell survival by inhibiting adaptation of the mitotic checkpoint. Thus, PKD/MFF-dependent mitochondrial fission is critical for the maintenance of genome integrity during cell division.
Mots clés
MFF, PKD, cell survival, fission, mitochondria, mitosis, mitotic checkpoint
Référence
Cell Rep. 2021 May 18;35(7):109129