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Updated: Apr 19, 2026

Assessment of Mitochondrial Fission/Fusion Dynamics in Kidney Proximal Tubular Cells
Published on: November 14, 2025
Transient assembly of F-actin on the outer mitochondrial membrane contributes to mitochondrial fission
Sunan Li1, Shan Xu1, Brian A Roelofs1
1Center for Biomedical Engineering and Technology, Department of Biochemistry and Molecular Biology, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201 Center for Biomedical Engineering and Technology, Department of Biochemistry and Molecular Biology, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201.
Abstract:
In addition to established membrane remodeling roles in various cellular locations, actin has recently emerged as a participant in mitochondrial fission. However, the underlying mechanisms of its participation remain largely unknown. We report that transient de novo F-actin assembly on the mitochondria occurs upon induction of mitochondrial fission and F-actin accumulates on the mitochondria without forming detectable submitochondrial foci. Impairing mitochondrial division through Drp1 knockout or inhibition prolonged the time of mitochondrial accumulation of F-actin and also led to abnormal mitochondrial accumulation of the actin regulatory factors cortactin, cofilin, and Arp2/3 complexes, suggesting that disassembly of mitochondrial F-actin depends on Drp1 activity. Furthermore, down-regulation of actin regulatory proteins led to elongation of mitochondria, associated with mitochondrial accumulation of Drp1. In addition, depletion of cortactin inhibited Mfn2 down-regulation- or FCCP-induced mitochondrial fragmentation. These data indicate that the dynamic assembly and disassembly of F-actin on the mitochondria participates in Drp1-mediated mitochondrial fission.
Insights
Actin dynamics on mitochondria are crucial for mitochondrial fission. This study reveals actin assembly and disassembly on mitochondria depend on Drp1 activity, impacting mitochondrial division.
Area of Science:
- Cell Biology
- Mitochondrial Dynamics
Background:
- Actin's role in membrane remodeling is established.
- Actin's involvement in mitochondrial fission is a recent discovery with unknown mechanisms.
Purpose of the Study:
- To elucidate the mechanisms of actin's participation in mitochondrial fission.
- To investigate the dynamic assembly and disassembly of F-actin on mitochondria during fission.
Main Methods:
- Induction of mitochondrial fission.
- Drp1 knockout and inhibition.
- Analysis of actin and actin regulatory factors (cortactin, cofilin, Arp2/3) on mitochondria.
- Down-regulation of actin regulatory proteins.
- Assessment of mitochondrial morphology and Drp1 localization.
Main Results:
- Transient de novo F-actin assembly occurs on mitochondria during fission.
- Impairing Drp1 activity prolonged F-actin accumulation and led to abnormal accumulation of actin regulatory factors.
- Disassembly of mitochondrial F-actin depends on Drp1 activity.
- Down-regulation of actin regulatory proteins caused mitochondrial elongation and Drp1 accumulation.
- Cortactin depletion inhibited mitochondrial fragmentation.
Conclusions:
- Dynamic assembly and disassembly of mitochondrial F-actin are integral to Drp1-mediated mitochondrial fission.
- Actin regulatory proteins play a role in regulating mitochondrial fission and dynamics.
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