Open Access Highly Accessed Research article

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

Mario D Cordero1,2,3†, Manuel De Miguel3†, Ana M Moreno Fernández3, Inés M Carmona López3, Juan Garrido Maraver1,2, David Cotán1,2, Lourdes Gómez Izquierdo4, Pablo Bonal5, Francisco Campa5,6, Pedro Bullon7, Plácido Navas1,2 and José A Sánchez Alcázar1,2*

  • * Corresponding author: José A Sánchez Alcázar jasanalc@upo.es

  • † Equal contributors

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Author affiliations

1 Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC, Ctra. de Utrera, km. 1, ISCIII, Sevilla 41013, Spain

2 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Universidad Pablo de Olavide-CSIC, Ctra. de Utrera, km. 1, ISCIII, Sevilla 41013, Spain

3 Dpto. Citología e Histología Normal y Patológica, Facultad de Medicina. Universidad de Sevilla, Avda. Dr. Fedriani s/n, Sevilla 41009, Spain

4 Departamento de Anatomía Patológica. Hospital Virgen del Rocío, Sevilla 41013, Spain

5 Dpto. de Medicina, Facultad de Medicina. Universidad de Sevilla, Avda. Dr. Fedriani s/n, Sevilla 41009, Spain

6 Distrito Sanitario Sevilla Sur., Facultad de Odontología, Universidad de Sevilla, Campus de los Perdigones, C/Avicena s/n, Sevilla 41009, Spain

7 Departamento de Periodontología, Facultad de Odontología, Universidad de Sevilla, Campus de los Perdigones, C/Avicena s/n, Sevilla 41009, Spain

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Citation and License

Arthritis Research & Therapy 2010, 12:R17 doi:10.1186/ar2918

Published: 28 January 2010

Abstract

Introduction

Fibromyalgia 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.

Methods

We 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.

Results

We 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.

Conclusions

These findings may support the role of oxidative stress and mitophagy in the pathophysiology of fibromyalgia.