Mitochondrial Dysfunction and Mitophagy Activation in Blood Mononuclear Cells of Fibromyalgia Patients: Implications in the Pathogenesis of the Disease

Overview

Journal Arthritis Res Ther

Publisher Biomed Central

Specialty Rheumatology

Date 2010 Jan 30

PMID 20109177

Citations 70

Authors

Mario D Cordero

Manuel de Miguel

Ana M Moreno Fernandez

Ines M Carmona Lopez

Juan Garrido Maraver

David Cotan

Lourdes Gomez Izquierdo

Pablo Bonal

Francisco Campa

Pedro Bullon

Placido Navas

Jose A Sanchez Alcazar

Affiliations

Soon will be listed here.

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.

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References

DiMauro S . Mitochondrial myopathies. Curr Opin Rheumatol. 2006; 18(6):636-41. DOI: 10.1097/01.bor.0000245729.17759.f2. View

Land J, Heales S, Duncan A, Hargreaves I . Some observations upon biochemical causes of ataxia and a new disease entity ubiquinone, CoQ10 deficiency. Neurochem Res. 2006; 32(4-5):837-43. DOI: 10.1007/s11064-006-9222-8. View

Ozgocmen S, Ozyurt H, Sogut S, Akyol O, Ardicoglu O, Yildizhan H . Antioxidant status, lipid peroxidation and nitric oxide in fibromyalgia: etiologic and therapeutic concerns. Rheumatol Int. 2005; 26(7):598-603. DOI: 10.1007/s00296-005-0079-y. View

Bazzichi L, Giannaccini G, Betti L, Fabbrini L, Schmid L, Palego L . ATP, calcium and magnesium levels in platelets of patients with primary fibromyalgia. Clin Biochem. 2008; 41(13):1084-90. DOI: 10.1016/j.clinbiochem.2008.06.012. View

Pieczenik S, Neustadt J . Mitochondrial dysfunction and molecular pathways of disease. Exp Mol Pathol. 2007; 83(1):84-92. DOI: 10.1016/j.yexmp.2006.09.008. View

Duncan A, Heales S, Mills K, Eaton S, Land J, Hargreaves I . Determination of coenzyme Q10 status in blood mononuclear cells, skeletal muscle, and plasma by HPLC with di-propoxy-coenzyme Q10 as an internal standard. Clin Chem. 2005; 51(12):2380-2. DOI: 10.1373/clinchem.2005.054643. View

Trounce I, Kim Y, Jun A, Wallace D . Assessment of mitochondrial oxidative phosphorylation in patient muscle biopsies, lymphoblasts, and transmitochondrial cell lines. Methods Enzymol. 1996; 264:484-509. DOI: 10.1016/s0076-6879(96)64044-0. View

Kim I, Rodriguez-Enriquez S, Lemasters J . Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys. 2007; 462(2):245-53. PMC: 2756107. DOI: 10.1016/j.abb.2007.03.034. View

Lambert A, Brand M . Reactive oxygen species production by mitochondria. Methods Mol Biol. 2009; 554:165-81. DOI: 10.1007/978-1-59745-521-3_11. View

10.

Cordero M, Moreno-Fernandez A, deMiguel M, Bonal P, Campa F, Jimenez-Jimenez L . Coenzyme Q10 distribution in blood is altered in patients with fibromyalgia. Clin Biochem. 2009; 42(7-8):732-5. DOI: 10.1016/j.clinbiochem.2008.12.010. View

11.

Haas R, Parikh S, Falk M, Saneto R, Wolf N, Darin N . The in-depth evaluation of suspected mitochondrial disease. Mol Genet Metab. 2008; 94(1):16-37. PMC: 2810849. DOI: 10.1016/j.ymgme.2007.11.018. View

12.

Levine B, Yuan J . Autophagy in cell death: an innocent convict?. J Clin Invest. 2005; 115(10):2679-88. PMC: 1236698. DOI: 10.1172/JCI26390. View

13.

Quinzii C, Lopez L, Von-Moltke J, Naini A, Krishna S, Schuelke M . Respiratory chain dysfunction and oxidative stress correlate with severity of primary CoQ10 deficiency. FASEB J. 2008; 22(6):1874-85. PMC: 2731482. DOI: 10.1096/fj.07-100149. View

14.

Manuel y Keenoy B, Moorkens G, Vertommen J, De Leeuw I . Antioxidant status and lipoprotein peroxidation in chronic fatigue syndrome. Life Sci. 2001; 68(17):2037-49. DOI: 10.1016/s0024-3205(01)01001-3. View

15.

Rodriguez-Enriquez S, Kim I, Currin R, Lemasters J . Tracker dyes to probe mitochondrial autophagy (mitophagy) in rat hepatocytes. Autophagy. 2006; 2(1):39-46. PMC: 4007489. DOI: 10.4161/auto.2229. View

16.

Jacobsen S, Danneskiold-Samsoe B . Dynamic muscular endurance in primary fibromyalgia compared with chronic myofascial pain syndrome. Arch Phys Med Rehabil. 1992; 73(2):170-3. View

17.

Kowaltowski A, de Souza-Pinto N, Castilho R, Vercesi A . Mitochondria and reactive oxygen species. Free Radic Biol Med. 2009; 47(4):333-43. DOI: 10.1016/j.freeradbiomed.2009.05.004. View

18.

Ozgocmen S, Ozyurt H, Sogut S, Akyol O . Current concepts in the pathophysiology of fibromyalgia: the potential role of oxidative stress and nitric oxide. Rheumatol Int. 2005; 26(7):585-97. DOI: 10.1007/s00296-005-0078-z. View

19.

Park J, Niermann K, Olsen N . Evidence for metabolic abnormalities in the muscles of patients with fibromyalgia. Curr Rheumatol Rep. 2000; 2(2):131-40. DOI: 10.1007/s11926-000-0053-3. View

20.

Quinzii C, DiMauro S, Hirano M . Human coenzyme Q10 deficiency. Neurochem Res. 2006; 32(4-5):723-7. PMC: 1832150. DOI: 10.1007/s11064-006-9190-z. View