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

Arthritis Res Ther. 2010;12(1):R17. doi: 10.1186/ar2918. Epub 2010 Jan 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / physiology*
  • Cell Separation
  • Chromatography, High Pressure Liquid
  • Female
  • Fibromyalgia / metabolism
  • Fibromyalgia / pathology*
  • Flow Cytometry
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / pathology*
  • Lipid Peroxidation / physiology
  • Male
  • Membrane Potential, Mitochondrial / physiology
  • Microscopy, Electron, Transmission
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Mitochondrial Proteins / metabolism
  • Oxidative Stress / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ubiquinone / analogs & derivatives
  • Ubiquinone / metabolism

Substances

  • Mitochondrial Proteins
  • Ubiquinone
  • coenzyme Q10