Mitochondrial complex activity in permeabilised cells of chronic fatigue syndrome patients using two cell types.
Tomas, Cara, Brown, Audrey E, Newton, Julia L et al. · PeerJ · 2019 · DOI
Quick Summary
This study looked at whether the powerhouses of cells (mitochondria) work differently in ME/CFS patients compared to healthy people. Researchers tested muscle cells and immune cells from the blood using a special technique to measure how well different parts of the mitochondrial energy-production system functioned. Surprisingly, they found no significant differences between ME/CFS patients and healthy controls, suggesting that if mitochondria aren't working properly in ME/CFS, the problem may occur before it reaches the mitochondria itself.
Why It Matters
Mitochondrial dysfunction is a leading hypothesis in ME/CFS pathophysiology. This study provides important negative evidence that challenges whether the core mitochondrial machinery itself is fundamentally broken, redirecting attention toward upstream regulatory or metabolic processes that might explain observed energy dysfunction in patients.
Observed Findings
No significant differences in Complex I activity between CFS and control groups in skeletal myotubes or PBMCs
No significant differences in Complex II activity between groups in either cell type
No significant differences in Complex IV activity between groups in either cell type
No significant differences in fatty acid oxidation-supported respiration between CFS patients and controls
No significant differences in glutaminolysis-supported respiration between groups
Inferred Conclusions
Previously observed mitochondrial dysfunction in whole PBMCs from CFS patients originates upstream of the mitochondrial respiratory chain rather than from intrinsic defects in complex activity
Individual mitochondrial respiratory chain complexes appear to have normal activity in both skeletal muscle and immune cells of ME/CFS patients
Mitochondrial dysfunction in ME/CFS, if present, may involve metabolic regulation, substrate delivery, or cellular signaling rather than the core machinery of oxidative phosphorylation
Remaining Questions
What upstream mechanisms (substrate availability, mitochondrial calcium dynamics, or regulatory signaling) might explain previously documented mitochondrial dysfunction in whole cells?
What This Study Does Not Prove
This study does not prove mitochondria function normally in ME/CFS—it specifically tested only the respiratory chain complexes and does not exclude mitochondrial dysfunction in other processes (calcium handling, protein synthesis, autophagy, or metabolic regulation). The study was also relatively small and did not examine mitochondrial biogenesis, quality control mechanisms, or the effects of exercise stress. Negative findings in two cell types do not exclude tissue-specific mitochondrial problems in other tissues.
Tags
Symptom:Fatigue
Biomarker:Blood Biomarker
Method Flag:Weak Case DefinitionSmall SampleExploratory Only
Do mitochondrial problems exist in other ME/CFS-relevant tissues (brain, heart, or gut) that were not examined in this study?
How do these findings reconcile with studies showing impaired mitochondrial respiration in whole CFS cells, and what specific cellular factors mediate that difference?
Could post-exercise mitochondrial dysfunction or stress-induced changes in mitochondrial function explain patient symptoms even if baseline complex activity is normal?