biomolecules: Bioenergetic and Proteomic Profiling of Immune Cells in ME/CFS Patients: An Exploratory Study - Fernandez-Guerra et al - 2021

biomolecules: Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study
Fernandes-Guerra et al

Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous, debilitating, and complex disease.

Along with disabling fatigue, ME/CFS presents an array of other core symptoms, including autonomic nervous system (ANS) dysfunction, sustained inflammation, altered energy metabolism, and mitochondrial dysfunction.

Here, we evaluated patients' symptomatology and the mitochondrial metabolic parameters in peripheral blood mononuclear cells (PBMCs) and plasma from a clinically well-characterised cohort of six ME/CFS patients compared to age- and gender-matched controls.

We performed a comprehensive cellular assessment using bioenergetics (extracellular flux analysis) and protein profiles (quantitative mass spectrometry-based proteomics) together with self-reported symptom measures of fatigue, ANS dysfunction, and overall physical and mental well-being.

This ME/CFS cohort presented with severe fatigue, which correlated with the severity of ANS dysfunction and overall physical well-being. PBMCs from ME/CFS patients showed significantly lower mitochondrial coupling efficiency.

They exhibited proteome alterations, including altered mitochondrial metabolism, centred on pyruvate dehydrogenase and coenzyme A metabolism, leading to a decreased capacity to provide adequate intracellular ATP levels.

Overall, these results indicate that PBMCs from ME/CFS patients have a decreased ability to fulfill their cellular energy demands.

 

This field is crying out for replication studies and (to my untrained, somewhat uninformed try) this is yet another study finding similar mitochondrial issues. Anyone got a good overview of these studies / seen a good review paper? Would be good to compare results / where in the ATP production process issus have been found / what types of cells were tested.

 

time and time again the same results, and nothing ever changes for us... we're still being treated as hypochondriacs and hysterical when some 8000 studies show that our bodies are a complete wreck, specially in regard to energy producing cellular systems . I just don't understand anymore what the point of these studies is, nothing ever, ever changes for us. So tired and frustrated...

 

A subunit the mitochondrial complex V was also abnormal. That's similar to the complex V inefficiency previously reported.

 

The biggest problem with studies like this is the assumption that patterns of glycolysis or mitochondrial respiration in PBMCs is somehow relevant, despite the fact that the microenvironment for PBMCs is quite different to other tissue types.

 

What do you think about this paper which opens up new hypotheses in the understanding of neuronal bioenergetics: Efficient extra-mitochondrial aerobic ATP synthesis in neuronal membrane systems - PubMed (nih.gov)

 

Ok so now multiple studies are showing a similar mitochondrial problem. Seems to me like normal energy production is impaired so we rely on backup energy systems (see mtor upregulation). Maybe, due to the inefficiency of those systems and the fact that they are meant to only be auxiliary and thus used sparingly, their overuse (as a result of intense physical / mental stimulation) leads to the production of damaging substances or direct cellular damage resulting in PEM?

 

FSMC can be accessed here. Not perfect but better than some I've seen.
https://www.sralab.org/sites/default/files/2017-06/Questionnaire_Kappos_et_al.php1_.pdf