Wang, Ping-Yuan, Ma, Jin, Kim, Young-Chae et al. · Proceedings of the National Academy of Sciences of the United States of America · 2023 · DOI
Researchers found that a protein called WASF3 may be responsible for exercise intolerance in ME/CFS by interfering with how mitochondria (the energy-producing parts of cells) work in muscles. When WASF3 levels were high, both mice and cells from ME/CFS patients showed reduced energy production capacity. Lowering WASF3 in the patient's cells improved their mitochondrial function, suggesting this protein could be a potential treatment target.
This study identifies a specific molecular mechanism that could explain the energy deficiency underlying exercise intolerance in ME/CFS, potentially opening new avenues for targeted treatment. The findings suggest that therapies targeting WASF3 or ER stress may help restore mitochondrial function and improve symptoms in ME/CFS and related fatigue conditions.
This study does not prove that WASF3 elevation is the sole or primary cause of ME/CFS in all patients, as it may represent one pathway among many. The work is primarily mechanistic and correlative; whether WASF3 reduction would clinically improve exercise intolerance in ME/CFS patients requires controlled clinical trials. The findings may not be generalizable to all ME/CFS presentations, given the heterogeneity 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
Wang, Ping-Yuan, Ma, Jin, Kim, Young-Chae, Son, Annie Y, Syed, Abu Mohammad, Liu, Chengyu, et al. (2023). WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome.. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.2302738120
BibTeX
@article{mecfsatlas-wang-2023-wasf3-disrupts,
author = {Wang, Ping-Yuan and Ma, Jin and Kim, Young-Chae and Son, Annie Y and Syed, Abu Mohammad and Liu, Chengyu and Mori, Mateus P and Huffstutler, Rebecca D and Stolinski, JoEllyn L and Talagala, S Lalith and Kang, Ju-Gyeong and Walitt, Brian T and Nath, Avindra and Hwang, Paul M},
title = {WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2023},
doi = {10.1073/pnas.2302738120},
note = {PubMed: 37579159},
url = {https://www.mecfsatlas.com/evidence/wang-2023-wasf3-disrupts},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/wang-2023-wasf3-disrupts
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