Mitochondrial dysfunction and mitophagy activation in Fibromyalgia

Dolphin

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Free full text at: http://arthritis-research.com/content/12/1/R17

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

Cordero MD, De Miguel M, Moreno Fernndez AM, Carmona Lpez IM, Garrido Maraver J, Cotn D, Gmez Izquierdo L, Bonal P, Campa F, Bullon P, Navas P, Snchez Alczar JA.

Arthritis Res Ther. 2010 Jan 28;12(1):R17. [Epub ahead of print]

Centro Andaluz de Biologa del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC, Ctra, de Utrera, km, 1, ISCIII, Sevilla 41013, Spain. jasanalc@upo.es.

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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It would be interesting to run the same tests on ME/CFS patients. There is still the view that FM and ME/CFS are different poles of the same disease.
 

Dolphin

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It would be interesting to run the same tests on ME/CFS patients. There is still the view that FM and ME/CFS are different poles of the same disease.
I agree. I think it was discussed in another thread but I reckon that a percentage of patients in Fibromyalgia studies have ME/CFS but there could be a wide variation in the percentages between differen centres.

I think researchers interested in ME/CFS could get lots of ideas from Fibromyalgia studies but at the same time there can be risks e.g. in Fibromyalgia, exercise is generally said to be helpful (I've seen studies which didn't find this but these tend to be forgotten about!) and also patients are said to be over-sensitive to pain (which perhaps may be true in some cases) while I think these theories can be problematic in ME/CFS (and indeed in Fibromyalgia, if the pain is actually from oxidative stress for example).
 

hvs

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Fascinating. Now we have to figure out how people's "disease beliefs" (or whatever the whackjob jargon is) causing their mitochondrial dysfunction??

<For the irony-challenged: this is a joke.>
 

spindrift

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Can anyone explain the terms 'autophagic genes' and 'mitophagy'?

My thoughts: 'self eating genes' and 'mito eating something?' seem a bit vague. :confused:

:confused::confused::confused::confused::confused:
 

Dr. Yes

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I hadn't seen the following paper, referenced in the study in question, before:

Vecchiet et al "Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome" (2002)

Abstract

In 21 patients with chronic fatigue syndrome (CFS) versus 20 normal subjects, we investigated the oxidant/antioxidant balance and its correlation with muscle symptoms. Patients versus controls showed significantly: lower Lag Phase and Vitamin E (Vit E) concentrations in plasma and low-density lipoproteins (LDL), higher LDL thiobarbituric acid reactive substances (TBARS), higher fatigue and lower muscle pain thresholds to electrical stimulation. A significant direct linear correlation was found between fatigue and TBARS, thresholds and Lag Phase, thresholds and Vit E in plasma and LDL. A significant inverse linear correlation was found between fatigue and Lag Phase, fatigue and Vit E, thresholds and TBARS. Increased oxidative stress and decreased antioxidant defenses are related to the extent of symptomatology in CFS, suggesting that antioxidant supplementation might relieve muscle symptoms in the syndrome.
Thought it might be of interest to someone...
 

Dr. Yes

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Can anyone explain the terms 'autophagic genes' and 'mitophagy'?

My thoughts: 'self eating genes' and 'mito eating something?' seem a bit vague. :confused:

:confused::confused::confused::confused::confused:

Hey spin,

From the full text of the paper:

Autophagy is a regulated lysosomal pathway involved in the degradation and recycling of cytoplasmic materials [38-42]. During autophagy, cytoplasmic materials are sequestered into double-membraned vesicles, 'autophagosomes', which then fuse with lysosomes to form autolysosomes, in which degradation of cellular structures occurs. Many cellular stresses can cause induction of autophagy, such as endoplasmic reticulum stress, mitochondrial dysfunction, or oxidative stress [42-44]. 'Mitophagy' was coined to describe the selective removal of mitochondria by autophagy during development and under pathologic conditions [36,45]....Autophagy can be beneficial for the cells by eliminating dysfunctional mitochondria, but massive autophagy can promote cell injury [41] and may contribute to the pathophysiology of FM.
"Autophagic genes" are genes that cause autophagy when they are activated.
 
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Gerwyn

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Interesting and necessary, IF!

Thanks for posting this, Tom.
sarah myhill has with even more profound effects excercise intolerance directly correlated with the degree of mitodysfunction as meaured by atp deficiency
 

spindrift

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So a recap in simple.wikipedia format:

In FM there is oxidative stress and mitochondrial dysfunction.

Duh!!!!

But I did learn a cool new word 'mitophagy'. Thanks for the help Dr. Yes.

@Gerwyn
Sarah Myhill rocks!
 
G

Gerwyn

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Fascinating. Now we have to figure out how people's "disease beliefs" (or whatever the whackjob jargon is) causing their mitochondrial dysfunction??

<For the irony-challenged: this is a joke.>
Is it not obvious? Mitochondria have abherrant beliefs as well.I know for a fact that this is true because Wesselly said so and he would never "distort the truth" would he?