Oncogenesis (Sep 2021)

The prohibitin-binding compound fluorizoline inhibits mitophagy in cancer cells

  • Sonia Núñez-Vázquez,
  • José Saura-Esteller,
  • Ismael Sánchez-Vera,
  • Emma Guilbaud,
  • Ana M. Cosialls,
  • Gabriel Pons,
  • Jean-Ehrland Ricci,
  • Daniel Iglesias-Serret,
  • Sandrine Marchetti,
  • Joan Gil

DOI
https://doi.org/10.1038/s41389-021-00352-9
Journal volume & issue
Vol. 10, no. 9
pp. 1 – 9

Abstract

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Abstract Fluorizoline is a prohibitin-binding compound that triggers apoptosis in several cell lines from murine and human origin, as well as in primary cells from hematologic malignancies by inducing the integrated stress response and ER stress. Recently, it was described that PHB (Prohibitin) 1 and 2 are crucial mitophagy receptors involved in mediating the autophagic degradation of mitochondria. We measured mitophagy in HeLa cells expressing Parkin and in A549, a lung cancer cell line that can undergo mitophagy in a Parkin-independent manner, and we demonstrated that both fluorizoline and rocaglamide A, another PHB-binding molecule, inhibit CCCP- and OA-induced mitophagy. Moreover, we demonstrated that PHBs are mediating Parkin-dependent mitophagy. In conclusion, besides being a potent pro-apoptotic compound, we present fluorizoline as a promising new mitophagy modulator that could be used as anticancer agent.