Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease

Mario D Cordero,Juan Garrido Maraver,David Cotán,Francisco Campa,José A Sánchez Alcázar,Inés M Carmona López,Pablo Bonal,Plácido Navas,Ana M Moreno Fernández,Lourdes Gómez Izquierdo,Pedro Bullon,Manuel De Miguel

doi:10.1186/ar2918

Abstract

IntroductionFibromyalgia is a chronic pain syndrome with unknown etiology. Recent studies have shown some evidence demonstrating that oxidative stress may have a role in the pathophysiology of fibromyalgia. However, it is still not clear whether oxidative stress is the cause or the effect of the abnormalities documented in fibromyalgia. Furthermore, the role of mitochondria in the redox imbalance reported in fibromyalgia also is controversial. We undertook this study to investigate the role of mitochondrial dysfunction, oxidative stress, and mitophagy in fibromyalgia.MethodsWe studied 20 patients (2 male, 18 female patients) from the database of the Sevillian Fibromyalgia Association and 10 healthy controls. We evaluated mitochondrial function in blood mononuclear cells from fibromyalgia patients measuring, coenzyme Q10 levels with high-performance liquid chromatography (HPLC), and mitochondrial membrane potential with flow cytometry. Oxidative stress was determined by measuring mitochondrial superoxide production with MitoSOX™ and lipid peroxidation in blood mononuclear cells and plasma from fibromyalgia patients. Autophagy activation was evaluated by quantifying the fluorescence intensity of LysoTracker™ Red staining of blood mononuclear cells. Mitophagy was confirmed by measuring citrate synthase activity and electron microscopy examination of blood mononuclear cells.ResultsWe found reduced levels of coenzyme Q10, decreased mitochondrial membrane potential, increased levels of mitochondrial superoxide in blood mononuclear cells, and increased levels of lipid peroxidation in both blood mononuclear cells and plasma from fibromyalgia patients. Mitochondrial dysfunction was also associated with increased expression of autophagic genes and the elimination of dysfunctional mitochondria with mitophagy.ConclusionsThese findings may support the role of oxidative stress and mitophagy in the pathophysiology of fibromyalgia.

Highlights

Fibromyalgia is a chronic pain syndrome with unknown etiology
Mitochondrial dysfunction was associated with increased expression of autophagic genes and the elimination of dysfunctional mitochondria with mitophagy
These findings may support the role of oxidative stress and mitophagy in the pathophysiology of fibromyalgia

Summary

Introduction

Recent studies have shown some evidence demonstrating that oxidative stress may have a role in the pathophysiology of fibromyalgia. Fibromyalgia (FM) is a common chronic pain syndrome accompanied by other symptoms such as fatigue, headache, sleep disturbances, and depression. We detected decreased coenzyme Q10 (CoQ10) levels and increased reactive oxygen species (ROS) production in blood mononuclear cells of FM patients, providing direct evidence of increased oxidative stress at the cellular level [5]. CoQ10 deficiency induces decreased activities of complex II + III, complex III and complex IV, reduced expression of mitochondrial proteins involved in oxidative phosphorylation, decreased mitochondrial membrane potential, increased production of reactive oxygen species (ROS), activation of mitochondrial permeability transition (MPT), mitophagy of dysfunctional mitochondria, and reduced growth rates [8,9]

Objectives

Methods

Results

Discussion

Conclusion