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Updated: Sep 16, 2025

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Dynamin-like Proteins Combine Mechano-constriction and Membrane Remodeling to Enable Two-Step Mitochondrial Fission

Haleh Alimohamadi1,2,3,4, Elizabeth Wei-Chia Luo1,2,3,4, Xiaoying Liu5

  • 1Department of Bioengineering, University of California, Los Angeles, Los Angeles, California 90025, United States.

Journal of the American Chemical Society
|July 8, 2025
PubMed

Insights

Mitochondrial fission relies on dynamin-like proteins (DLPs). This study reveals how DLPs

Area of Science:

  • Biochemistry
  • Cell Biology
  • Biophysics

Background:

  • Mitochondrial fission, crucial for cellular function, is regulated by dynamin-like proteins (DLPs).
  • Dysregulation of DLPs is linked to various diseases, highlighting their importance.
  • The precise mechanical mechanisms underlying DLP-mediated membrane fission remain incompletely understood.

Purpose of the Study:

  • To elucidate the multiscale mechanical phenomena governing dynamin-related protein 1 (Drp1)-mediated mitochondrial membrane fission.
  • To investigate the synergistic roles of DLP assembly, disassembly, and membrane remodeling in fission.

Main Methods:

  • Developed a mechanical model of Drp1, calibrated with small-angle X-ray scattering data.
  • Integrated machine learning analysis of the Drp1 sequence.
  • Validated the model using optogenetic mechanostimulation of mitochondria in live cells.

Main Results:

  • Identified a 'snap-through instability' triggered by free DLPs, driving membrane shape transitions.
  • Demonstrated that DLP activity induces a shift from cylindrical to catenoid-shaped membrane necks.
  • Found that the fission pathway critically depends on the length of the confined membrane tube.

Conclusions:

  • The interplay between dynamin-like protein assembly and disassembly dictates diverse scission pathways.
  • A unified mechanical framework explains how Drp1 activity drives mitochondrial fission.
  • This research provides critical insights into the biophysics of membrane fission and its disease relevance.

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