Tag: mitochondrial stress

Indistinguishable mitochondrial phenotypes after exposure of healthy myoblasts to myalgic encephalomyelitis/chronic fatigue syndrome or control serum

Abstract:

Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome is a disease of uncertain aetiology that affects up to 400,000 individuals in the UK. Exposure of cultured cells to the sera of people with ME has been proposed to cause phenotypic changes in these cells in vitro when compared to sera from healthy controls. ME serum factors causing these changes could inform the development of diagnostic tests.

In this study, we performed a large-scale, pre-registered replication of an experiment from Fluge et al (2016) that reported an increase in maximal respiratory capacity in healthy myoblasts after treatment with serum from people with ME compared to serum from healthy controls.

We replicated the original experiment with a larger sample size, using sera from 67 people with ME and 53 controls to treat healthy cultured myoblasts, and generated results from over 1,700 mitochondrial stress tests performed with a Seahorse Bioanalyser. We observed no significant differences between treatment with ME or healthy control sera for our primary outcome of interest, oxygen consumption rate at maximal respiratory capacity.

Results from our study provide strong evidence against the hypothesis that ME blood factors differentially affect healthy myoblast mitochondrial phenotypes in vitro.

Source: Ryback AA, Hillier CB, Loureiro CM, Ponting CP, Dalton CF. Indistinguishable mitochondrial phenotypes after exposure of healthy myoblasts to myalgic encephalomyelitis/chronic fatigue syndrome or control serum. PLoS One. 2026 Feb 3;21(2):e0341334. doi: 10.1371/journal.pone.0341334. PMID: 41632778; PMCID: PMC12867253. https://pmc.ncbi.nlm.nih.gov/articles/PMC12867253/ (Full text)

Temporal dynamics of the plasma proteomic landscape reveals maladaptation in ME/CFS following exertion

Abstract:

The overarching symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is post-exertional malaise (PEM), an exacerbation of symptoms following physical or mental exertion. To investigate the molecular underpinnings of PEM, we performed longitudinal plasma proteomics using the Somascan® 7K aptamer-based assay to monitor 6,361 unique plasma proteins in 132 individuals (96 females and 36 males) subjected to two maximal cardiopulmonary exercise tests separated by a 24-hour recovery period.

The cohort included 79 ME/CFS cases compared to 53 age- and BMI-matched sedentary controls, allowing us to distinguish disease-specific molecular alterations from those due to physical deconditioning. Longitudinal profiling revealed widespread proteomic changes following exertion, with the most pronounced alterations observed in ME/CFS participants during the recovery phase, coinciding with the onset of PEM.

Compared to controls, ME/CFS subjects showed persistent dysregulation of immune, metabolic, and neuromuscular pathways. Key findings included suppression of T and B cell signaling, downregulation of IL-17 and cell-cell communication pathways, and upregulation of glycolysis/gluconeogenesis, suggestive of mitochondrial stress and impaired immune recovery from exercise. Proteomic associations with physiological performance (VO2max, anaerobic threshold) revealed disruptions between protein abundance and exercise capacity in ME/CFS versus controls.

Correlations with symptom severity linked changes in immune-related proteins and ME/CFS symptoms including muscle pain, recurrent sore throat, and lymph node tenderness. Sex-stratified analyses revealed distinct molecular responses between females and males, emphasizing the importance of considering sex as a biological variable in ME/CFS research.

Finally, our analysis of sedentary controls contributes new data of molecular responses to acute exertion in a predominantly female sedentary cohort, a population historically underrepresented in exercise physiology studies. Together, these findings underscore the value of dynamic, proteomic profiling over time for characterizing maladaptive responses to exertion in ME/CFS and provide a foundation for deeper mechanistic investigation into PEM.

Source: Germain A, Glass KA, Eckert MA, Giloteaux L, Hanson MR. Temporal dynamics of the plasma proteomic landscape reveals maladaptation in ME/CFS following exertion. Mol Cell Proteomics. 2025 Nov 12:101467. doi: 10.1016/j.mcpro.2025.101467. Epub ahead of print. PMID: 41237904. https://www.mcponline.org/article/S1535-9476(25)00566-3/fulltext (Full text)