Mitochondrial Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
Syed, Abu Mohammad, Karius, Alexander K, Ma, Jin et al. · Physiology (Bethesda, Md.) · 2025 · DOI
Quick Summary
This review examines how mitochondria—the parts of cells that produce energy—may not be working properly in ME/CFS patients. The authors suggest that problems with energy production in cells could explain why people with ME/CFS feel severely exhausted after physical activity. They also note that similar energy problems appear in long COVID, which suggests both conditions may share a common underlying cause.
Why It Matters
Understanding mitochondrial dysfunction in ME/CFS is crucial because it offers a potential biological explanation for the debilitating fatigue and post-exertional malaise that characterize the illness, potentially opening new avenues for diagnosis and treatment. The connection between ME/CFS and long COVID mitochondrial dysfunction suggests findings in one condition may inform research and therapeutic strategies in the other, affecting millions of patients globally.
Observed Findings
- Mitochondrial dysfunction and impaired energy production have been identified in cellular and biochemical studies of ME/CFS patients.
- Post-exertional malaise, a hallmark symptom of ME/CFS, correlates with evidence of energy metabolism abnormalities following exertion.
- Similar mitochondrial dysfunction patterns appear in long COVID patients, suggesting a shared pathophysiological mechanism between the two conditions.
- Impaired oxidative phosphorylation and ATP synthesis have been observed in patient-derived cells and tissues.
Inferred Conclusions
- Mitochondrial dysfunction likely plays a significant role in the pathogenesis of ME/CFS, particularly in explaining post-exertional malaise.
- The shared mitochondrial abnormalities in ME/CFS and long COVID suggest these conditions may have overlapping biological mechanisms.
- Further research into mitochondrial dysfunction could identify new biomarkers and therapeutic targets for both disorders.
Remaining Questions
- Is mitochondrial dysfunction the primary cause of ME/CFS, or is it secondary to other underlying pathophysiological processes?
- What specific molecular mechanisms lead to mitochondrial dysfunction in ME/CFS, and how do they differ from other conditions affecting energy metabolism?
- Can mitochondrial function be restored or improved, and would doing so ameliorate ME/CFS symptoms, particularly post-exertional malaise?
- How do genetic, infectious, and inflammatory factors interact with mitochondrial dysfunction in ME/CFS pathogenesis?
What This Study Does Not Prove
As a review article, this study does not present new experimental evidence and cannot definitively prove that mitochondrial dysfunction causes ME/CFS—only that evidence suggests an association. The review cannot establish whether mitochondrial problems are a primary cause, a secondary consequence of illness, or one of multiple contributing factors. Individual studies cited may show correlation rather than causation, and findings in cell cultures or animal models may not fully translate to human ME/CFS patients.
Topics
Tags
Metadata
- DOI
- 10.1152/physiol.00056.2024
- PMID
- 39960432
- Review status
- Editor reviewed
- Evidence level
- Early hypothesis, preprint, editorial, or weak support
- Last updated
- 7 April 2026