Related Experiment Video

Updated: Nov 5, 2025

A Faster, High Resolution, mtPA-GFP-based Mitochondrial Fusion Assay Acquiring Kinetic Data of Multiple Cells in Parallel Using Confocal Microscopy
10:45

A Faster, High Resolution, mtPA-GFP-based Mitochondrial Fusion Assay Acquiring Kinetic Data of Multiple Cells in Parallel Using Confocal Microscopy

Published on: July 20, 2012

16.8K

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

Evanthia Pangou1, Olga Bielska1, Lucile Guerber1

  • 1Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France; Centre National de la Recherche Scientifique UMR 7104, Strasbourg, France; Institut National de la Santé et de la Recherche Médicale U964, Strasbourg, France; Université de Strasbourg, Strasbourg, France.

Cell Reports
|May 19, 2021
PubMed

Insights

Protein Kinase D (PKD) phosphorylates the mitochondrial fission factor (MFF) during mitosis, driving mitochondrial fission. This process is vital for chromosome segregation and maintaining genome integrity during cell division.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Mitochondria are dynamic organelles undergoing fission and fusion.
  • Mitotic mitochondrial fission is essential for equitable organelle distribution to daughter cells.
  • The precise role of mitochondrial fission in actively driving mitotic progression is not well understood.

Purpose of the Study:

  • To investigate the pathway linking mitochondrial fission to mitotic progression in mammalian cells.
  • To identify the molecular mechanisms regulating mitochondrial fission during mitosis.

Main Methods:

  • Western blotting and immunoprecipitation to detect protein phosphorylation.
  • Cellular imaging to observe mitochondrial morphology and dynamics.
  • Mitotic checkpoint assays to assess cell cycle progression.
  • Genetic manipulation to study the roles of MFF and PKD.

Main Results:

  • Protein Kinase D (PKD) directly phosphorylates the mitochondrial fission factor (MFF) during mitosis.
  • PKD-dependent MFF phosphorylation is necessary and sufficient for mitochondrial fission in mitotic cells.
  • This phosphorylation event is specific to mitosis and does not occur in interphase cells.
  • MFF phosphorylation is critical for proper chromosome segregation and cell survival.
  • The process inhibits adaptation of the mitotic checkpoint, preventing premature exit from mitosis.

Conclusions:

  • A novel pathway involving PKD/MFF-dependent mitochondrial fission regulates mitotic progression.
  • This pathway is critical for ensuring genome integrity during cell division.
  • Targeting this pathway could have implications for understanding and treating diseases associated with genomic instability.
Keywords:
MFFPKDcell survivalfissionmitochondriamitosismitotic checkpoint

More Related Videos

Using Scaffold Liposomes to Reconstitute Lipid-proximal Protein-protein Interactions In Vitro08:53

Using Scaffold Liposomes to Reconstitute Lipid-proximal Protein-protein Interactions In Vitro

Published on: January 11, 2017

9.1K
Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk113:15

Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1

Published on: February 25, 2016

12.1K

Related Concept Videos

M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.8K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
6.8K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.3K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.8K
Molecular Factors Affecting Cell Division01:27

Molecular Factors Affecting Cell Division

Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
3.5K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
9.5K