Cell Reports (May 2021)

A PKD-MFF signaling axis couples mitochondrial fission to mitotic progression

  • Evanthia Pangou,
  • Olga Bielska,
  • Lucile Guerber,
  • Stephane Schmucker,
  • Arantxa Agote-Arán,
  • Taozhi Ye,
  • Yongrong Liao,
  • Marta Puig-Gamez,
  • Erwan Grandgirard,
  • Charlotte Kleiss,
  • Yansheng Liu,
  • Emmanuel Compe,
  • Zhirong Zhang,
  • Ruedi Aebersold,
  • Romeo Ricci,
  • Izabela Sumara

Journal volume & issue
Vol. 35, no. 7
p. 109129

Abstract

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Summary: 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.

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