Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Centre for Human Metabolomics, North-West University, Potchefstroom, South Africa.
PLoS One. 2020 Apr 10;15(4):e0231136. doi: 10.1371/journal.pone.0231136. eCollection 2020.
Myalgic encephalomyelitis/ Chronic fatigue syndrome (ME/CFS) has been associated with abnormalities in mitochondrial function. In this study we have analysed previous bioenergetics data in peripheral blood mononuclear cells (PBMCs) using new techniques in order to further elucidate differences between ME/CFS and healthy control cohorts. We stratified our ME/CFS cohort into two individual cohorts representing moderately and severely affected patients in order to determine if disease severity is associated with bioenergetic function in PBMCs. Both ME/CFS cohorts showed reduced mitochondrial function when compared to a healthy control cohort. This shows that disease severity does not correlate with mitochondrial function and even those with a moderate form of the disease show evidence of mitochondrial dysfunction. Equations devised by another research group have enabled us to calculate ATP-linked respiration rates and glycolytic parameters. Parameters of glycolytic function were calculated by taking into account respiratory acidification. This revealed severely affected ME/CFS patients to have higher rates of respiratory acidification and showed the importance of accounting for respiratory acidification when calculating parameters of glycolytic function. Analysis of previously published glycolysis data, after taking into account respiratory acidification, showed severely affected patients have reduced glycolysis compared to moderately affected patients and healthy controls. Rates of ATP-linked respiration were also calculated and shown to be lower in both ME/CFS cohorts. This study shows that severely affected patients have mitochondrial and glycolytic impairments, which sets them apart from moderately affected patients who only have mitochondrial impairment. This may explain why these patients present with a more severe phenotype.
肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）与线粒体功能异常有关。在这项研究中，我们使用新技术分析了外周血单核细胞（PBMC）中的先前生物能量学数据，以进一步阐明 ME/CFS 与健康对照组之间的差异。我们将 ME/CFS 队列分层为两个单独的队列，代表中度和重度受影响的患者，以确定疾病严重程度是否与 PBMC 中的生物能量功能相关。与健康对照组相比，两个 ME/CFS 队列的线粒体功能均降低。这表明疾病严重程度与线粒体功能无关，即使是患有中度疾病的患者也表现出线粒体功能障碍的证据。另一个研究小组设计的方程使我们能够计算 ATP 连接的呼吸率和糖酵解参数。通过考虑呼吸酸化来计算糖酵解功能的参数。这表明严重受影响的 ME/CFS 患者具有更高的呼吸酸化率，并表明在计算糖酵解功能参数时考虑呼吸酸化的重要性。在考虑呼吸酸化后，对先前发表的糖酵解数据进行分析表明，与中度受影响的患者和健康对照组相比，严重受影响的患者的糖酵解减少。还计算了 ATP 连接的呼吸率，结果表明两个 ME/CFS 队列的呼吸率均较低。这项研究表明，严重受影响的患者存在线粒体和糖酵解损伤，这使他们与仅存在线粒体损伤的中度受影响的患者区分开来。这可能解释了为什么这些患者表现出更严重的表型。
