A study just published in October 2017 by PhD student (and ME/CFS patient) Cara Tomas finds that mitochondrial oxidative phosphorylation is functioning well under par in ME/CFS patients at baseline, and that when ME/CFS patients' cells need to generate extra energy in order to cope with increased physiological stress, these cells are less able to ramp up their energy production to meet the higher energy demands. So ME/CFS patients' mitochondria are not able to produce enough energy at baseline, and these mitochondria have additional problems when trying to ramp up energy production when higher energy output is required. The published paper by Cara Tomas is here: Cellular bioenergetics is impaired in patients with chronic fatigue syndrome The Tomas study analyzed in vitro the energy metabolism of ME/CFS patient's peripheral blood mononuclear cells (PBMCs), using a commercial laboratory machine (called the Seahorse XFe96 Analyzer) which is specially designed to measure cell energy metabolism (thus this study should be reproducible by anyone with such a machine). Interestingly, although oxidative phosphorylation was impaired in ME/CFS, glycolysis in ME/CFS patients' cells was found to be normal. Baseline energy output from anaerobic glycolysis in ME/CFS patients' cells was the same as the healthy control cells; and also the glycolysis stress test (where cells need to ramp up their glycolytic energy production to meet higher energy demands) showed that glycolysis in ME/CFS patients' cells is able to increase energy output when required, just as effectively as healthy control cells. So in ME/CFS, glycolysis is working normally at baseline, and is perfectly able to increase energy output when required. Whereas oxidative phosphorylation was found impaired on both counts. The findings of this study by Tomas broadly match up with the results of the Myhill, Booth and McLaren-Howard energy metabolism studies, which found that ME/CFS patients have impaired mitochondria oxidative phosphorylation (as well as impairments in the transport of ADP and ATP in an out of the mitochondria, and other impairments). This Tomas study I think (but am not sure) would also be consistent with Fluge and Mella's metabolic profiling study. Fluge and Mella's results suggested an impairment of pyruvate dehydrogenase (PDH), which is an enzyme that couples glycolysis with oxidative phosphorylation. When burning glucose for energy, glucose is first processed by glycolysis (situated outside the mitochondria), and then the energy production process is handed over to the mitochondria, where oxidative phosphorylation completes the job. With an impairment in pyruvate dehydrogenase, there is a partial blockage in this handover, meaning that oxidative phosphorylation does not get a chance to do its job (so from the Fluge and Mella perspective, in ME/CFS oxidative phosphorylation might be fully functional, but does not get a chance to function properly because it is not handed over what it needs). However, oxidative phosphorylation can also burn fats for energy, and fat burning does not rely on glycolysis or pyruvate dehydrogenase, so even if PDH were impaired, it would not alter the fat burning capabilities of oxidative phosphorylation in the mitochondria. So this raises a question mark as to whether in the Tomas study, oxidative phosphorylation was running on the glucose or fat energy production pathway. The Tomas study does talk about adding glucose solution to the cells, which suggests that in this study the energy source oxidative phosphorylation is running on is glucose rather than fats. In which case, the impairment that Tomas found in oxidative phosphorylation could be due to an impairment of pyruvate dehydrogenase, making the Tomas study consistent with the Fluge and Mella paper. An article about the Tomas study is found here. And a thread discussing an earlier poster presentation by Cara Tomas is found here.