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Allosteric control of dynamin-related protein 1-catalyzed mitochondrial fission through a conserved disordered

Isabel Pérez-Jover1,2, Kristy Rochon3, Di Hu4

  • 1Department of Biochemistry and Molecular Biology, University of the Basque Country, 48940 Leioa, Spain.

Research Square
|July 28, 2023
PubMed

Insights

The dynamin-related protein 1 (Drp1) C-terminal motif (CT-SLiM) allosterically regulates mitochondrial fission. This motif controls Drp1 function by modulating GTPase activity and subunit dynamics, impacting mitochondrial morphology in vivo.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Dynamin-related protein 1 (Drp1) is crucial for mitochondrial fission.
  • Regulatory mechanisms of Drp1-mediated mitochondrial fission are not fully understood.

Purpose of the Study:

  • To investigate the role of the Drp1 C-terminus in regulating mitochondrial fission.
  • To elucidate the allosteric mechanisms controlling Drp1 function.

Main Methods:

  • In vitro biochemical assays to study Drp1 structure and function.
  • In vivo studies using genetic manipulation of the Drp1 CT-SLiM.
  • Analysis of Drp1 subunit dynamics and GTP hydrolysis.

Main Results:

  • A conserved six-residue Short Linear Motif (CT-SLiM) at the Drp1 C-terminus acts as a critical allosteric site.
  • CT-SLiM regulates Drp1 structure, subunit dynamics, and GTPase activity.
  • Modifications to CT-SLiM impair mitochondrial fission in vitro and in vivo.

Conclusions:

  • Drp1-catalyzed mitochondrial fission is regulated by allosteric communication via the CT-SLiM.
  • Deceleration of GTPase activity and altered assembly dynamics are key to fission regulation.
  • Findings challenge existing models of Drp1 function in mitochondrial dynamics.
Keywords:
Dynamin-related protein 1intrinsically disordered domainmitochondrial fission

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