There is a European study that has checked for the expression of 1007 mitochondrial proteins in platelets from 2 twins, one with ME/CFS and the other one healthy (Ciregia F et al 2016). Of these proteins, 194 were significantly modified in the sick twin, in comparison with the healthy one. I have checked for differences in pyruvate dehydrogenase complex, ADP/ATP translocase subunits and pyruvate dehydrogenase kinases. This is what I have found in these two twins:
1) Pyruvate dehydrogenase E1 subunits alpha (PDHA) and beta are both increased in the sick twin, which is in partial agreement with the increase in PDHA found by Fluge and Mella (Fluge et al. 2016);
2) ADP/ATP translocase, subunit 2 and 3, are low in the sick twin, compared with the healthy one, which could be in accordance with the study by Myhill and colleagues (Myhill S et al. 2009), (Booth, N et al 2012), if only we assume that the problem with this enzyme found in group defined “HiBlk” is not due to blockage from a molecule or an autoantibody, but is instead due to underexpression of the enzyme itself;
3) Pyruvate dehydrogenase kinases 1 and 3 are overexpressed, which again is in partial agreement with what Fluge and Mella have found in their recent paper, where PDK 1, 2, 4 are overexpressed in ME/CFS patients.
In conclusion, the sick twin does not seem to have any blockage of ADP/ATP translocase, because if that was the case he would present an overexpression of the enzyme, while the enzyme is underexpressed. On the other hand, he does seem to have a problem with his pyruvate dehydrogenase, in fact there is inhibition by overexpressed PDK 1 and 3 and – at the same time – he is expressing more PDHA than his healthy twin.
The same European study (Ciregia F et al 2016) then selected three enzymes from the 194 significantly modified in the sick twin: ACON, ATPB e MDHM. They then evaluated the expression of these enzymes in a cohort of 45 Italian patients with ME/CFS and in 45 matched controls. In this case, they considered mitochondria from saliva. They found that both ACON and ATPB are overexpressed in patients.
ACON stands for aconitase, which is an enzyme of the TCA cycle, that catalyzes the step from citrate to cis-aconitate (see figure). Thus, its over-expression in this cohort of patients is in agreement with the depletion of these two metabolites, found in a recent Japanese study (Yamano E, et al. 2016) and with the study by Fluge and Mella: in fact, if we assume that the TCA cycle is poorly supplied by glycolysis, it would overexpress one or more enzymes in order to increase the energy production from the substrate available. Thus, this finding seems in agreement with both the Norwegian and the Japanese study and seems to complete the picture.
ATPB is subunit beta of ATP synthase, and it is involved in the last step of mitochondrial metabolism, the conversion of ADP into ATP. Again, an overexpression of this enzyme seems to be in agreement with poor energy supply.
A discussion on these observations can be found in this thread in Phoenix Rising.