Journal Article

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

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

2018

Overview

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.

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