The Bacterial Protein CNF1 as a Potential Therapeutic Strategy against Mitochondrial Diseases: A Pilot Study.

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.

• Authors: Alessia Fabbri, Sara Travaglione, Zaira Maroccia, Marco Guidotti, Ciro Leonardo Pierri, Guido Primiano, Serenella Servidei, Stefano Loizzo, Carla Fiorentini
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 19 Issue 7 (06 21 2018) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 29933571 (Publication Type: Case Reports, Journal Article)

Chemical References

• Bacterial Toxins
• DNA, Mitochondrial
• Escherichia coli Proteins
• Membrane Transport Proteins
• Mitochondrial Precursor Protein Import Complex Proteins
• Receptors, Cell Surface
• TOMM20 protein, human
• cytotoxic necrotizing factor type 1
• Adenosine Triphosphate
• Electron Transport Complex IV

Topics

• Adenosine Triphosphate (biosynthesis)
• Bacterial Toxins (isolation & purification, pharmacology)
• DNA, Mitochondrial (genetics, metabolism)
• Electron Transport Complex IV (genetics, metabolism)
• Escherichia coli (chemistry)
• Escherichia coli Proteins (isolation & purification, pharmacology)
• Fibroblasts (drug effects, metabolism, pathology)
• Gene Expression
• Humans
• MERRF Syndrome (drug therapy, genetics, metabolism, pathology)
• Male
• Membrane Transport Proteins (genetics, metabolism)
• Middle Aged
• Mitochondria (drug effects, genetics, metabolism, ultrastructure)
• Mitochondrial Precursor Protein Import Complex Proteins
• Mutation
• Pilot Projects
• Primary Cell Culture
• Receptors, Cell Surface (genetics, metabolism)
• Stress Fibers (drug effects, metabolism, ultrastructure)