Missailidis, Daniel, Sanislav, Oana, Allan, Claire Y et al. · International journal of molecular sciences · 2021 · DOI
This study looked at how cells from ME/CFS patients use energy differently than healthy cells. Researchers found that ME/CFS cells are overproducing enzymes that break down fats, amino acids, and other nutrients to fuel their mitochondria (the cell's power plants), while their glycolysis (the main way cells normally produce energy) stays normal. This suggests ME/CFS cells may be forced to use alternative, less efficient pathways to generate the energy they need.
This research identifies a potential metabolic bottleneck in ME/CFS—cells appear to be compensating for inefficient mitochondrial function by overworking alternative fuel pathways. Understanding this dysregulation could guide development of targeted metabolic therapies and explain why patients experience energy depletion despite apparently normal glycolysis.
This study demonstrates cellular pathway dysregulation in lymphoblasts but does not establish causation or prove these metabolic changes occur in all ME/CFS tissues or drive the full clinical syndrome. The findings are correlative and based on cultured cell lines, which may not fully represent the complex in vivo metabolic environment. It does not demonstrate whether these changes are a cause or consequence of ME/CFS pathology.
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
Missailidis, Daniel, Sanislav, Oana, Allan, Claire Y, Smith, Paige K, Annesley, Sarah J, & Fisher, Paul R (2021). Dysregulated Provision of Oxidisable Substrates to the Mitochondria in ME/CFS Lymphoblasts.. International journal of molecular sciences. https://doi.org/10.3390/ijms22042046
BibTeX
@article{mecfsatlas-missailidis-2021-dysregulated-provision,
author = {Missailidis, Daniel and Sanislav, Oana and Allan, Claire Y and Smith, Paige K and Annesley, Sarah J and Fisher, Paul R},
title = {Dysregulated Provision of Oxidisable Substrates to the Mitochondria in ME/CFS Lymphoblasts.},
journal = {International journal of molecular sciences},
year = {2021},
doi = {10.3390/ijms22042046},
note = {PubMed: 33669532},
url = {https://www.mecfsatlas.com/evidence/missailidis-2021-dysregulated-provision},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/missailidis-2021-dysregulated-provision
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