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

Cordero, Mario D.; Miguel, Manuel de; Fernández, Antonio J. Sánchez; López, Inés M Carmona; Garrido-Maraver, Juan; Cotán, David; Izquierdo, Lourdes Gómez; Bonal, Pablo; Campa, Francisco; Bullón, Pedro; Navas, Plácido; Sánchez-Alcázar, José Antonio

doi:10.1186/ar2918

Cited by 136 publications

(144 citation statements)

References 43 publications

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“…In this sense, enhancing basal muscle tone (e.g., through multicomponent exercise programs) could potentially improve resting-state functional connectivity in sensory-motor systems and reduce peripheral sensitization and clinical pain, which warrants further research. Similarly, peripheral mechanisms (e.g., abnormalities in microcirculatory capillaries [35] or irregularities in mitochondria [36]) might reduce peripheral tissue oxygenation and lead to central sensitization in FM patients. Thus, increasing tissue oxygenation as a result of aerobic exercise could potentially diminish peripheral and central sensitization and reduce clinical pain (3).…”

Section: Discussionmentioning

confidence: 99%

Association of Physical Fitness With Pain in Women With Fibromyalgia: The al‐Ándalus Project

Soriano‐Maldonado

Ruiz

Aparicio

et al. 2015

Arthritis Care & Research

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Objective. This population-based cross-sectional study aimed to characterize the association of different components of physical fitness with pain levels, pain-related catastrophizing, and chronic pain self-efficacy in women with fibromyalgia (FM). Methods. A total of 468 women with FM participated. The experience of pain was assessed with different tools (algometry, a numeric rating scale [revised FM impact questionnaire], a visual analog scale, and the bodily pain subscale on the Short Form 36 health survey). We also assessed pain-related catastrophizing and chronic pain self-efficacy. Physical fitness was assessed with performance-based tests (Senior Fitness Test battery and handgrip dynamometry). A standardized composite score was computed for each component of physical fitness (aerobic fitness, muscle strength, flexibility, and motor agility), and their average comprised a clustered global fitness profile. Results. Overall, higher physical fitness was consistently associated with lower levels of pain, lower pain-related catastrophizing, and higher chronic pain self-efficacy (regardless of the pain assessment method and the fitness test evaluated). Muscle strength and flexibility were independently associated with pain (P < 0.005 for both), and participants with high muscle strength plus high flexibility (combined effect) had the lowest levels of pain in this population. Aerobic fitness and flexibility were independently associated with pain-related catastrophizing (P < 0.001 for both) and chronic pain self-efficacy (P < 0.001 for both), and participants with high flexibility plus high aerobic fitness (combined effect) had the best catastrophizing and self-efficacy profiles. Conclusion. Our results suggest that higher physical fitness is associated with lower levels of pain, lower pain-related catastrophizing, and higher chronic pain self-efficacy in women with FM. These results might have implications for future intervention studies in this population.

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Section: Discussionmentioning

confidence: 99%

Association of Physical Fitness With Pain in Women With Fibromyalgia: The al‐Ándalus Project

Soriano‐Maldonado

Ruiz

Aparicio

et al. 2015

Arthritis Care & Research

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“…Ten nuclear genes involved in CoQ biosynthesis have been identified in humans and disease-causing mutations, which lead to primary CoQ deficiency, have been identified in some of these genes [25]. Secondary CoQ deficiency has been identified in a wide range of diseases, including mitochondrial diseases, neurodegenerative diseases, such as Parkinson's disease, cancer, fibromyalgia, and in patients undergoing statin treatment [22,26,27]. Currently, primary and secondary CoQ deficiencies are the focus of some attention, due to the high prevalence of the latter, and the potential for treatment.…”

Section: Discussionmentioning

confidence: 99%

Recovery of MERRF Fibroblasts and Cybrids Pathophysiology by Coenzyme Q10

et al. 2012

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Mitochondrial DNA mutations are an important cause of human disease for which there is no effective treatment. Myoclonic epilepsy with ragged-red fibers (MERRF) is a mitochondrial disease usually caused by point mutations in transfer RNA genes encoded by mitochondrial DNA. The most common mutation associated with MERRF syndrome, m.8344A>G in the gene MT-TK, which encodes transfer RNA Lysine , affects the translation of all mitochondrial DNA encoded proteins. This impairs the assembly of the electron transport chain complexes leading to decreased mitochondrial respiratory function. Here we report on how this mutation affects mitochondrial function in primary fibroblast cultures established from patients harboring the A8344G mutation. Coenzyme Q 10 (CoQ) levels, as well as mitochondrial respiratory chain activity, and mitochondrial protein expression levels were significantly decreased in MERRF fibroblasts. Mitotracker staining and imaging analysis of individual mitochondria indicated the presence of small, rounded, depolarized mitochondria in MERRF fibroblasts. Mitochondrial dysfunction was associated with increased oxidative stress and increased degradation of impaired mitochondria by mitophagy. Transmitochondrial cybrids harboring the A8344G mutation also showed CoQ deficiency, mitochondrial dysfunction, and increased mitophagy activity. All these abnormalities in patient-derived fibroblasts and cybrids were partially restored by CoQ supplementation, indicating that these cell culture models may be suitable for screening and validation of novel drug candidates for MERRF disease.

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“…This is clinically important since mitochondrial dysfunction can initiate a series of cellular events that promote pro-inflammatory signaling pathways or lead to cell death. Several studies have characterized mitochondrial function of peripheral blood mononuclear cells and platelets in conditions such as fibromyalgia, diabetes, septic shock, and Alzheimer's disease [3][4][5][6][7] . For example, a recent study evaluated the bioenergetics of platelets as a marker for mitochondrial function and found that platelets from Type 2 diabetic patients had diminished mitochondrial oxygen consumption 7,8 .…”

Section: Introductionmentioning

confidence: 99%

Bioenergetics and the Oxidative Burst: Protocols for the Isolation and Evaluation of Human Leukocytes and Platelets

Kramer

Chacko

Ravi

et al. 2014

JoVE

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Mitochondrial dysfunction is known to play a significant role in a number of pathological conditions such as atherosclerosis, diabetes, septic shock, and neurodegenerative diseases but assessing changes in bioenergetic function in patients is challenging. Although diseases such as diabetes or atherosclerosis present clinically with specific organ impairment, the systemic components of the pathology, such as hyperglycemia or inflammation, can alter bioenergetic function in circulating leukocytes or platelets. This concept has been recognized for some time but its widespread application has been constrained by the large number of primary cells needed for bioenergetic analysis. This technical limitation has been overcome by combining the specificity of the magnetic bead isolation techniques, cell adhesion techniques, which allow cells to be attached without activation to microplates, and the sensitivity of new technologies designed for high throughput microplate respirometry. An example of this equipment is the extracellular flux analyzer. Such instrumentation typically uses oxygen and pH sensitive probes to measure rates of change in these parameters in adherent cells, which can then be related to metabolism. Here we detail the methods for the isolation and plating of monocytes, lymphocytes, neutrophils and platelets, without activation, from human blood and the analysis of mitochondrial bioenergetic function in these cells. In addition, we demonstrate how the oxidative burst in monocytes and neutrophils can also be measured in the same samples. Since these methods use only 8-20 ml human blood they have potential for monitoring reactive oxygen species generation and bioenergetics in a clinical setting.

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

Cited by 136 publications

References 43 publications

Association of Physical Fitness With Pain in Women With Fibromyalgia: The al‐Ándalus Project

Association of Physical Fitness With Pain in Women With Fibromyalgia: The al‐Ándalus Project

Recovery of MERRF Fibroblasts and Cybrids Pathophysiology by Coenzyme Q10

Bioenergetics and the Oxidative Burst: Protocols for the Isolation and Evaluation of Human Leukocytes and Platelets

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