Missailidis, Daniel, Annesley, Sarah J, Allan, Claire Y et al. · International journal of molecular sciences · 2020 · DOI
Researchers studied the energy-producing structures (mitochondria) in blood cells from ME/CFS patients and found a specific problem: the cells have difficulty using a protein complex called Complex V that normally makes ATP, the body's energy currency. To compensate, the cells turn up their other energy-making machinery, which keeps ATP levels normal while resting but may leave the cells exhausted when they need to produce extra energy quickly—similar to running a car engine at maximum capacity just to maintain normal speed.
This study identifies a specific mitochondrial defect in ME/CFS patients—Complex V inefficiency—and explains a potential mechanism for post-exertional malaise: cells may be unable to meet acute energy demands because their compensatory pathways are already maximally activated at rest. Understanding this molecular abnormality could guide development of targeted treatments and validates the long-suspected role of mitochondrial dysfunction in ME/CFS pathology.
This study does not prove that Complex V deficiency causes ME/CFS or that it occurs in all patients, as it examined only immortalized lymphoblasts from a single timepoint. The findings correlate with ME/CFS diagnosis but cannot establish causation or demonstrate whether this defect is primary, secondary, or tissue-specific. Additionally, the study does not show whether correcting Complex V function would improve patient symptoms.
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, Annesley, Sarah J, Allan, Claire Y, Sanislav, Oana, Lidbury, Brett A, Lewis, Donald P, et al. (2020). An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients.. International journal of molecular sciences. https://doi.org/10.3390/ijms21031074
BibTeX
@article{mecfsatlas-missailidis-2020-isolated-complex,
author = {Missailidis, Daniel and Annesley, Sarah J and Allan, Claire Y and Sanislav, Oana and Lidbury, Brett A and Lewis, Donald P and Fisher, Paul R},
title = {An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients.},
journal = {International journal of molecular sciences},
year = {2020},
doi = {10.3390/ijms21031074},
note = {PubMed: 32041178},
url = {https://www.mecfsatlas.com/evidence/missailidis-2020-isolated-complex},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/missailidis-2020-isolated-complex
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