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Comparative Analysis of Septin Modifiers, Forchlorfenuron and UR214-9, on Mitochondrial Fragmentation and Lytic Cell
Dominik Brokatzky1,2, Rajdeep Das1, Hannah Painter1
1Department of Infection Biology, London School of Hygiene & Tropical Medicine, London, UK.
Cytoskeleton (Hoboken, N.J.)
|August 29, 2025
Summary
Septin modifiers like FCF and UR214-9 disrupt mitochondrial integrity and cause cell death in macrophages. These findings offer insights into inflammatory diseases and potential new medicines.
Area of Science:
- Cell Biology
- Immunology
- Pharmacology
Background:
- Septins are crucial GTP-binding proteins involved in cell division, mitochondrial dynamics, and immune responses.
- Pharmacological tools to modulate septin function are limited, hindering research into their roles in human health.
- Forchlorfenuron (FCF) was the first identified septin modifier, impacting mitochondrial organization.
Purpose of the Study:
- To compare the effects of Forchlorfenuron (FCF) and its more potent analog, UR214-9, on mitochondrial integrity and cell death.
- To investigate the in vitro effects of FCF and UR214-9 in macrophages and their in vivo effects in zebrafish larvae.
- To explore the potential of septin modifiers in understanding and treating inflammatory diseases.
Main Methods:
- In vitro studies using macrophages exposed to FCF and UR214-9.
- In vivo studies utilizing zebrafish larvae treated with FCF and UR214-9.
- Assessment of mitochondrial fragmentation, mitochondrial mass, SEPT7 expression, cell death, and caspase-1 activity.
Main Results:
- Both FCF and UR214-9 induced dose-dependent mitochondrial fragmentation in macrophages without affecting mitochondrial mass or SEPT7 expression.
- FCF and UR214-9 triggered lytic cell death in LPS-primed macrophages.
- In zebrafish larvae, both compounds showed dose-dependent toxicity, with UR214-9 being more toxic; FCF induced macrophage cell death and caspase-1 activity.
Conclusions:
- Septin modifiers FCF and UR214-9 significantly impact mitochondrial integrity and macrophage survival.
- These compounds can induce lytic cell death in macrophages, suggesting a role in inflammatory processes.
- Further research into septin modifiers could lead to novel therapeutic strategies for inflammatory diseases.
