Smits, Bart, van den Heuvel, Lambert, Knoop, Hans et al. · Mitochondrion · 2011 · DOI
This study looked at whether measurements of mitochondria (the energy-producing parts of cells) can help distinguish ME/CFS from true mitochondrial diseases. The researchers found that while people with ME/CFS have fewer mitochondria overall, the mitochondria that are present work normally. In contrast, people with actual mitochondrial disorders have mitochondria that don't function well, even when mitochondrial numbers are considered.
This research provides an objective biochemical tool to differentiate ME/CFS from primary mitochondrial diseases, which is clinically important since the two conditions require different management approaches. The finding that mitochondrial enzymes function normally in ME/CFS despite reduced mitochondrial numbers suggests a different underlying mechanism than true mitochondrial disorders, potentially opening new avenues for understanding ME/CFS pathophysiology.
This study does not prove that reduced mitochondrial content causes ME/CFS symptoms—it only demonstrates an association. The findings are limited to muscle tissue and may not reflect mitochondrial dysfunction in other tissues or cellular compartments relevant to ME/CFS. The study also does not establish whether the reduced mitochondrial content is a primary defect or a secondary consequence of the disease.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Smits, Bart, van den Heuvel, Lambert, Knoop, Hans, Küsters, Benno, Janssen, Antoon, Borm, George, et al. (2011). Mitochondrial enzymes discriminate between mitochondrial disorders and chronic fatigue syndrome.. Mitochondrion. https://doi.org/10.1016/j.mito.2011.05.005
BibTeX
@article{mecfsatlas-smits-2011-mitochondrial-enzymes,
author = {Smits, Bart and van den Heuvel, Lambert and Knoop, Hans and Küsters, Benno and Janssen, Antoon and Borm, George and Bleijenberg, Gijs and Rodenburg, Richard and van Engelen, Baziel},
title = {Mitochondrial enzymes discriminate between mitochondrial disorders and chronic fatigue syndrome.},
journal = {Mitochondrion},
year = {2011},
doi = {10.1016/j.mito.2011.05.005},
note = {PubMed: 21664495},
url = {https://www.mecfsatlas.com/evidence/smits-2011-mitochondrial-enzymes},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-25. https://www.mecfsatlas.com/evidence/smits-2011-mitochondrial-enzymes
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