Mitochondrial enzymes discriminate between mitochondrial disorders and chronic fatigue syndrome

Smits, B.W.; Heuvel, Lambert van den; Knoop, Hans; Küsters, Benno; Janssen, A.J.M.; Borm, George F.; Bleijenberg, Gijs; Rodenburg, Richard J.; Engelen, B.G.M. van

doi:10.1016/j.mito.2011.05.005

Cited by 61 publications

(62 citation statements)

References 26 publications

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“…Interestingly, reduced citrate synthase activity has been reported in ME/CFS patients. 4,31 A reduction in citrate provides for the loss of allosteric regulation to inhibit glycolysis and facilitate glucose to be re-directed to the pentose phosphate pathway for NADPH production, which is essential for fatty acid synthesis. This pathway also compromises the availability of glutathione to remove hydrogen peroxide and may contribute to the evaluation of free radical, low fatty acids and high oxidized LDL antibodies reported in ME/CFS patients.…”

Section: Cd56mentioning

confidence: 99%

“…32 Alternatively, reduced glycolytic reserve in combination with reduced citrate synthase activity may promote pyruvate to be converted into lactate and removed from the cell. 4,19,31 This is essential as the accumulation of pyruvate may result in inhibition of glycolysis. ME/CFS patients have reported increased blood lactate, muscular lactate and ventricular lactate.…”

Section: Cd56mentioning

confidence: 99%

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Reduced glycolytic reserve in isolated natural killer cells from Myalgic encephalomyelitis/chronic fatigue syndrome patients: A preliminary investigation

Nguyen

Staines

Johnston

et al. 2018

Asian Pac J Allergy Immunol

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Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is medically unexplained post-exertional fatigue associated with significant reduction in natural killer cell (NK) cytotoxicity activity. Cytotoxic activity relies on glycolytic flux and mitochondrial respiration to fulfill energetic cellular demands. While mitochondrial dysfunction has been reported in ME/CFS patients, no previous investigation has examined the bioenergetic profile of isolated NK cells from ME/CFS patients.

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Section: Cd56mentioning

confidence: 99%

Section: Cd56mentioning

confidence: 99%

Reduced glycolytic reserve in isolated natural killer cells from Myalgic encephalomyelitis/chronic fatigue syndrome patients: A preliminary investigation

Nguyen

Staines

Johnston

et al. 2018

Asian Pac J Allergy Immunol

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“…Four of the 5 patients had elevated resting lactate levels, which may help differentiate CFS from mitochondrial disorders, at least as an initial screening test. In the 4 patients on whom muscle immunohistochemistry was performed, the percentage of ragged-red fibers or cyclooxygenase-negative fibers was significantly elevated [19,90], which is not observed in CFS [91]. Many, but not all, patients with mitochondrial diseases have chronic fatigue but, in all likelihood, only a small fraction of those with CFS have a mitochondrial disorder.…”

Section: Chronic Fatiguementioning

confidence: 85%

“…This study cannot determine if the fatigue was caused by the low CS value or if the lower mitochondrial content as determined by the CS value was the effect of less-than-normal physical activity. However, ATP production rate was normal in CFS, suggesting the individual mitochondria function normally [91].…”

Section: Chronic Fatiguementioning

confidence: 95%

Neuromuscular and Systemic Presentations in Adults: diagnoses beyond MERRF and MELAS

Cohen

2013

Neurotherapeutics

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Mitochondrial diseases are a diverse group of inherited and acquired disorders that result in inadequate energy production. They can be caused by inheritable genetic mutations, acquired somatic mutations, and exposure to toxins (including some prescription medications). Normal mitochondrial physiology is responsible, in part, for the aging process itself, as free radical production within the mitochondria results in a lifetime burden of oxidative damage to DNA, especially the mitochondrial DNA that, in turn, replicate the mutational burden in future copies of itself, and lipid membranes. Primary mitochondrial diseases are those caused by mutations in genes that encode for mitochondrial structural and enzymatic proteins, and those proteins required for mitochondrial assembly and maintenance. A number of common adult maladies are associated with defective mitochondrial energy production and function, including diabetes, obesity, hyperthyroidism, hypothyroidism, and hyperlipidemia. Mitochondrial dysfunction has been demonstrated in many neurodegenerative disorders, including Alzheimer's disease, Parkinson disease, amyotrophic lateral sclerosis, and some cancers. Polymorphisms in mitochondrial DNA have been linked to disease susceptibility, including death from sepsis and survival after head injury. There is considerable overlap in symptoms caused by primary mitochondrial diseases and those illnesses that affect mitochondrial function, but are not caused by primary mutations, as well as disorders that mimic mitochondrial diseases, but are caused by other identified mutations. Evaluation of these disorders is complex, expensive, and not without false-negative and false-positive results that can mislead the physician. Most of the common heritable mitochondrial disorders have been well-described in the literature, but can be overlooked by many clinicians if they are uneducated about these disorders. In general, the evaluation of the classic mitochondrial disorders has become straightforward if the clinician recognized the phenotype and orders appropriate confirmatory testing. However, the majority of patients referred for a mitochondrial evaluation do not have a clear presentation that allows for rapid identification and testing. This article provides introductory comments on mitochondrial structure, physiology, and genetics, but will focus on the presentation and evaluation of adults with mitochondrial symptoms, but who may not have a primary mitochondrial disease.

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“…[21] Mitochondrial levels and dysfunction have also been related directly to chronic fatigue syndrome severity in multiple studies. [22][23][24] The second clinical outcome, obesity as measured by the body mass index (BMI; weight [kg]/height[m] 2 ) is also related to mitochondrial dysfunction. Twin studies involving discordant BMI have demonstrated lower levels of mitochondrial function involving the obese twin.…”

Section: Introductionmentioning

confidence: 99%

Fatigue and body mass index in the Fragile X premutation carrier

Summers

Cogswell

Goodrich

et al. 2014

Fatigue: Biomedicine, Health & Behavior

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Background: Recent evidence has shown that mitochondrial dysfunction may be significant in carriers of the Fragile X premutation. Purpose: The present study examined fatigue severity and body mass index (BMI) (two possible outcomes related to mitochondrial dysfunction) in premutation carriers with and without the Fragile X-associated Tremor Ataxia Syndrome (FXTAS) as compared to controls. Methods: Surveys to gather data on height and weight and fatigue impact (Fatigue Severity Scale) were sent out to previous research trial participants with Fragile X premutation-related disorders. Results: On the Fatigue Severity Scale, carriers with and without FXTAS had mean scores of 4.5 (SD 1.9) and 3.8 (SD 1.6), respectively, that differed significantly (p < 0.001) from the control mean score of 2.9 (SD 1.4). The mean BMI of carriers with FXTAS was 29.6 kg/m 2 (SD 5.3) which differed significantly (p = 0.003) from the mean BMI of carriers without FXTAS of 26.9 kg/m 2 (SD 5.1) and controls 26.7 kg/m 2 (SD 4.4). However, premutation carriers without FXTAS did not differ significantly in BMI from controls. Conclusions: The present study suggests potentially important clinical outcomes that may be related to the mitochondrial dysfunction seen in molecular studies previously done with premutation carriers.

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Mitochondrial enzymes discriminate between mitochondrial disorders and chronic fatigue syndrome

Cited by 61 publications

References 26 publications

Reduced glycolytic reserve in isolated natural killer cells from Myalgic encephalomyelitis/chronic fatigue syndrome patients: A preliminary investigation

Reduced glycolytic reserve in isolated natural killer cells from Myalgic encephalomyelitis/chronic fatigue syndrome patients: A preliminary investigation

Neuromuscular and Systemic Presentations in Adults: diagnoses beyond MERRF and MELAS

Fatigue and body mass index in the Fragile X premutation carrier

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