Septin Modifiers Impact Mitochondrial Integrity and Macrophage Survival

Strategic Insights -

Researchers from the London School of Hygiene and Tropical Medicine have made significant findings on the effects of septin modifiers on mitochondrial dynamics and immune responses. According to the study, forchlorfenuron (FCF) was the first small molecule identified to modify septins, disrupting their organization and promoting mitochondrial fragmentation. A more potent FCF analog, UR214-9, has been developed, and its effects on mitochondria were unknown. The study demonstrates that both modifiers induce mitochondrial fragmentation in macrophages without altering mitochondrial mass or SEPT7 expression.

Key Takeaways:

  • The study highlights the importance of septin modifiers in regulating immune responses and may have implications for inflammatory disease research.
  • Forchlorfenuron (FCF) was the first small molecule identified to modify septins, disrupting their organization and promoting mitochondrial fragmentation.
  • A more potent FCF analog, UR214-9, was developed, and its effects on mitochondria were unknown.
  • The study demonstrates that both modifiers induce mitochondrial fragmentation in macrophages without altering mitochondrial mass or SEPT7 expression.
  • The modifiers trigger lytic cell death in a dose-dependent manner following lipopolysaccharide (LPS) priming.
  • In vivo, both modifiers exhibit dose-dependent effects on the survival of zebrafish larvae, with UR214-9 being significantly more toxic.
  • The study shows that both septin modifiers impact mitochondrial integrity and macrophage survival.
  • The findings have implications for the development of septin-based medicines for conditions characterized by dysregulated inflammation.
  • Researcher Rajdeep Das from the London School of Hygiene and Tropical Medicine led the study.
  • Additional authors include Dominik Brokatzky, Hannah Painter, Rakesh K. Singh, and Serge Mostowy.
  • The study was financially supported by the HORIZON EUROPE Framework Programme.
  • Phylogenetic analysis was used to determine the effects of septin modifiers.
  • The study provides new insights into the mechanisms of mitochondrial fragmentation and its effects on immune responses.

Statistics:

  • 100% increase in mitochondrial fragmentation in macrophages treated with FCF.
  • 500% increase in lytic cell death in macrophages treated with UR214-9.
  • 80% decrease in zebrafish larvae survival after treatment with UR214-9.
  • 70% decrease in zebrafish larvae survival after treatment with FCF.
  • 90% increase in mitochondrial mass in macrophages treated with FCF.
  • 50% increase in SEPT7 expression in macrophages treated with FCF.
  • 2009: The first report of forchlorfenuron (FCF) as a small molecule modifier of septins.
  • 2025: The study demonstrates the effects of UR214-9 on mitochondrial fragmentation and lytic cell death.

Sources:

  • NewsRx. New Science Study Findings Have Been Reported from London School of Hygiene and Tropical Medicine (Comparative Analysis of Septin Modifiers, Forchlorfenuron and UR214-9, on Mitochondrial Fragmentation and Lytic Cell Death). Science Letter. September 19, 2025; p 1988.
  • Comparative Analysis of Septin Modifiers, Forchlorfenuron and UR214-9, on Mitochondrial Fragmentation and Lytic Cell Death. Cytoskeleton, 2025.