Tomas Cara, Brown Audrey, Strassheim Victoria, Elson Joanna L, Newton Julia, Manning Philip
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
PLoS One. 2017 Oct 24;12(10):e0186802. doi: 10.1371/journal.pone.0186802. eCollection 2017.
Chronic fatigue syndrome (CFS) is a highly debilitating disease of unknown aetiology. Abnormalities in bioenergetic function have been cited as one possible cause for CFS. Preliminary studies were performed to investigate cellular bioenergetic abnormalities in CFS patients. A series of assays were conducted using peripheral blood mononuclear cells (PBMCs) from CFS patients and healthy controls. These experiments investigated cellular patterns in oxidative phosphorylation (OXPHOS) and glycolysis. Results showed consistently lower measures of OXPHOS parameters in PBMCs taken from CFS patients compared with healthy controls. Seven key parameters of OXPHOS were calculated: basal respiration, ATP production, proton leak, maximal respiration, reserve capacity, non-mitochondrial respiration, and coupling efficiency. While many of the parameters differed between the CFS and control cohorts, maximal respiration was determined to be the key parameter in mitochondrial function to differ between CFS and control PBMCs due to the consistency of its impairment in CFS patients found throughout the study (p≤0.003). The lower maximal respiration in CFS PBMCs suggests that when the cells experience physiological stress they are less able to elevate their respiration rate to compensate for the increase in stress and are unable to fulfil cellular energy demands. The metabolic differences discovered highlight the inability of CFS patient PBMCs to fulfil cellular energetic demands both under basal conditions and when mitochondria are stressed during periods of high metabolic demand.
慢性疲劳综合征(CFS)是一种病因不明的高度致残性疾病。生物能量功能异常被认为是CFS的一个可能病因。进行了初步研究以调查CFS患者的细胞生物能量异常。使用来自CFS患者和健康对照者的外周血单个核细胞(PBMC)进行了一系列测定。这些实验研究了氧化磷酸化(OXPHOS)和糖酵解中的细胞模式。结果显示,与健康对照相比,取自CFS患者的PBMC中OXPHOS参数的测量值持续较低。计算了OXPHOS的七个关键参数:基础呼吸、ATP产生、质子泄漏、最大呼吸、储备能力、非线粒体呼吸和偶联效率。虽然CFS组和对照组之间的许多参数存在差异,但由于在整个研究中发现CFS患者的最大呼吸受损具有一致性(p≤0.003),因此最大呼吸被确定为CFS和对照PBMC之间线粒体功能不同的关键参数。CFS患者PBMCs中较低的最大呼吸表明,当细胞经历生理应激时,它们提高呼吸速率以补偿应激增加的能力较弱,并且无法满足细胞的能量需求。发现的代谢差异突出了CFS患者PBMCs在基础条件下以及在高代谢需求期间线粒体受到应激时无法满足细胞能量需求的情况。