A systematic review of mitochondrial abnormalities in ME/CFS/systemic exertion intolerance disease, 2020, Holden et al.

Sly Saint

Sly Saint

Senior Member (Voting Rights)
A systematic review of mitochondrial abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease
Abstract
Background

Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or Systemic Exertion Intolerance Disease (SEID) present with a constellation of symptoms including debilitating fatigue that is unrelieved by rest. The pathomechanisms underlying this illness are not fully understood and the search for a biomarker continues, mitochondrial aberrations have been suggested as a possible candidate. The aim of this systematic review is to collate and appraise current literature on mitochondrial changes in ME/CFS/SEID patients compared to healthy controls.

Methods
Embase, PubMed, Scopus and Medline (EBSCO host) were systematically searched for articles assessing mitochondrial changes in ME/CFS/SEID patients compared to healthy controls published between January 1995 and February 2020. The list of articles was further refined using specific inclusion and exclusion criteria. Quality and bias were measured using the Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies.

Results
Nineteen studies were included in this review. The included studies investigated mitochondrial structural and functional differences in ME/CFS/SEID patients compared with healthy controls. Outcomes addressed by the papers include changes in mitochondrial structure, deoxyribonucleic acid/ribonucleic acid, respiratory function, metabolites, and coenzymes.

Conclusion
Based on the included articles in the review it is difficult to establish the role of mitochondria in the pathomechanisms of ME/CFS/SEID due to inconsistencies across the studies. Future well-designed studies using the same ME/CFS/SEID diagnostic criteria and analysis methods are required to determine possible mitochondrial involvement in the pathomechanisms of ME/CFS/SEID.
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https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02452-3
 
I was very disappointed in this review paper. It started off well describing the method and techniques but I felt it lacked substance.

It would have been much more powerful if they had split the review into different topics. There were a lot of metabolomics studies which are not actually studying mitochondria. Even in that topic it is important to split blood metabolomics vs cellular metabolmics ie.. intracellular vs extracellular. Have a separate discussion about that.

One very important study did not make the final round and I don't know why. Item 43, The Stanford Xiannan Wang lab that found energy production was upregulated. This team are considered expert mito researchers. That paper also highlighted that the samples they received were PBMC cells and not in plasma/serum. The cells were put in culture and then treated for a long time.. They concluded that the finding of higher energy might be "more ATP is produced by non-mitochondrial sources.". That is certainly an area that could do with being investigated. They also said "Future studies are warranted to unravel why and how non-mitochondrial ATP production is activated in some patients, which will yield insights into novel strategies to address the pathological causes.". So yes, why not look at the high ATP subset of patients and see what can be learned about them in particular.
Paper : Elevated energy production in chronic fatigue syndrome patients

I thought the paper was missing a discsussion about the fact that presence of plasma/serum may play a role and finding a way to test the effect of plasma on mitochondria is a good avenue of study to pursue in the future.

They could have discussed new techniques such as the high power optical microscopes that allow real time visualisation of mitochondria.

Conclusion
Based on the included articles in the review it is difficult to establish the role of mitochondria in the pathomechanisms of ME/CFS/SEID due to inconsistencies across the studies. Future well-designed studies using the same ME/CFS/SEID diagnostic criteria and analysis methods are required to determine possible mitochondrial involvement in the pathomechanisms of ME/CFS/SEID.
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The general conclusions are useless. Specify which diagnostic criteria to use. We need to look at different cells types and differing techniques until we find a clue, and not just repeat another PBMC Seahorse test. Why not pick low or high ATP groups of patients and do a longitudinal study. Look at the effect on mitochondria in and out of plasma. Lets have formal intracelluar proteomics and metabolomics to see what Mito components are upregulated and downregulated.
 
wigglethemouse said:
The Stanford Xiannan Wang lab that found energy production was upregulated. This team are considered expert mito researchers.
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Just to quantify that statement. This is from the Xinnan Wang Lab website
The goal of our research at the Xinnan Wang Lab is to understand the regulatory mechanisms controlling mitochondrial dynamics and function and the mechanisms by which even subtle perturbations of these processes may contribute to neurodegenerative disorders.
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