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Updated: Nov 23, 2025
Analysis of Apoptosis in Zebrafish Embryos by Whole-mount Immunofluorescence to Detect Activated Caspase 3
Published on: December 20, 2013
Fluorizoline-induced apoptosis requires prohibitins in nematodes and human cells
José Saura-Esteller1, Ismael Sánchez-Vera1, Sonia Núñez-Vázquez1
1Departament de Ciències Fisiològiques, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona-IDIBELL (Institut d'Investigació Biomèdica de Bellvitge), L'Hospitalet de Llobregat, Barcelona, Spain.
Abstract:
We previously showed that fluorizoline, a fluorinated thiazoline compound, binds to both subunits of the mitochondrial prohibitin (PHB) complex, PHB1 and PHB2, being the expression of these proteins required for fluorizoline-induced apoptosis in mouse embryonic fibroblasts. To investigate the conservation of this apoptotic mechanism, we studied the effect of PHB downregulation on fluorizoline activity on two human cell lines, HEK293T and U2OS. Then, we asked whether PHBs mediate the effect of fluorizoline in a multicellular organism. Interestingly, reduced levels of PHBs in the human cells impaired the induction of apoptosis by fluorizoline. We observed that fluorizoline has a detrimental dose-dependent effect on the development and survival of the nematode model Caenorhabditis elegans. Besides, such effects of fluorizoline treatment in living nematodes were absent in PHB mutants. Finally, we further explored the apoptotic pathway triggered by fluorizoline in human cell lines. We found that the BH3-only proteins NOXA, BIM and PUMA participate in fluorizoline-induced apoptosis and that the induction of NOXA and PUMA is dependent on PHB expression.
Insights
Fluorizoline induces apoptosis by targeting the prohibitin (PHB) complex in human cells and C. elegans. PHB protein levels are crucial for fluorizoline
Area of Science:
- Cellular and Molecular Biology
- Apoptosis Research
- Drug Discovery and Development
Background:
- Fluorizoline, a fluorinated thiazoline compound, was previously shown to induce apoptosis in mouse cells by binding to the mitochondrial prohibitin (PHB) complex.
- The expression of PHB1 and PHB2 subunits is essential for this fluorizoline-induced apoptotic effect.
Purpose of the Study:
- To investigate the evolutionary conservation of the PHB-mediated apoptotic mechanism induced by fluorizoline.
- To determine if prohibitin proteins mediate fluorizoline's effects in human cell lines and a multicellular organism.
- To further elucidate the apoptotic pathway triggered by fluorizoline.
Main Methods:
- Downregulation of prohibitin (PHB) levels in human cell lines (HEK293T, U2OS) to assess fluorizoline's apoptotic activity.
- Treatment of the nematode model Caenorhabditis elegans with fluorizoline to evaluate its effects on development and survival.
- Analysis of PHB mutant nematodes to determine the role of PHBs in fluorizoline's effects.
- Investigation of BH3-only proteins (NOXA, BIM, PUMA) in the fluorizoline-induced apoptotic pathway in human cells.
Main Results:
- Reduced PHB levels in human cells impaired fluorizoline-induced apoptosis.
- Fluorizoline exhibited a dose-dependent detrimental effect on C. elegans development and survival.
- These detrimental effects in C. elegans were abolished in PHB mutants.
- NOXA, BIM, and PUMA were identified as key players in fluorizoline-induced apoptosis.
- The induction of NOXA and PUMA by fluorizoline was dependent on PHB expression.
Conclusions:
- The prohibitin complex is conserved as a mediator of fluorizoline-induced apoptosis across species.
- PHB proteins are essential for fluorizoline's detrimental effects on development and survival in C. elegans.
- Fluorizoline triggers apoptosis in human cells via BH3-only proteins NOXA and PUMA, with PHB expression being critical for their induction.
