The bacterial protein CNF1 as a potential therapeutic strategy against mitochondrial diseases: A pilot study

Alessia Fabbri, Sara Travaglione, Zaira Maroccia, Marco Guidotti, Ciro Leonardo Pierri, Guido Primiano, Serenella Servidei, Stefano Loizzo, Carla Fiorentini

Research output: Contribution to journalArticle

Abstract

The Escherichia coli protein toxin cytotoxic necrotizing factor 1 (CNF1), which acts on the Rho GTPases that are key regulators of the actin cytoskeleton, is emerging as a potential therapeutic tool against certain neurological diseases characterized by cellular energy homeostasis impairment. In this brief communication, we show explorative results on the toxin’s effect on fibroblasts derived from a patient affected by myoclonic epilepsy with ragged-red fibers (MERRF) that carries a mutation in the m.8344A>G gene of mitochondrial DNA. We found that, in the patient’s cells, besides rescuing the wild-type-like mitochondrial morphology, CNF1 administration is able to trigger a significant increase in cellular content of ATP and of the mitochondrial outer membrane marker Tom20. These results were accompanied by a profound F-actin reorganization in MERRF fibroblasts, which is a typical CNF1-induced effect on cell cytoskeleton. These results point at a possible role of the actin organization in preventing or limiting the cell damage due to mitochondrial impairment and at CNF1 treatment as a possible novel strategy against mitochondrial diseases still without cure.

Original languageEnglish
Article number1825
JournalInternational Journal of Molecular Sciences
Volume19
Issue number7
DOIs
Publication statusPublished - Jul 1 2018

Keywords

  • Actin cytoskeleton
  • Adenosine triphosphate
  • Cytotoxic necrotizing factor 1
  • Mitochondrial diseases
  • Myoclonic epilepsy with ragged red fibers syndrome

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    Fabbri, A., Travaglione, S., Maroccia, Z., Guidotti, M., Pierri, C. L., Primiano, G., Servidei, S., Loizzo, S., & Fiorentini, C. (2018). The bacterial protein CNF1 as a potential therapeutic strategy against mitochondrial diseases: A pilot study. International Journal of Molecular Sciences, 19(7), [1825]. https://doi.org/10.3390/ijms19071825