I tried very hard to see what her studies meant and they did not add up to anything I could make sense of.
It took me a week of reading and re-reading to begin to penetrate into these studies, party because I was not familiar with most of the biological pathways in these papers, and partly because there is a bit of complexity with the results they uncovered (they did not find a simple one-size-fits-all type of mitochondrial dysfunction in ME/CFS patients, but rather found a set of different mitochondrial dysfunctions, with each patient suffering from a subset of the dysfunctions — and in this way they have tentatively identified some subsets in ME/CFS).
Eventually I found the basic concepts of these studies seemed to make sense to me. For example, they found that oxidative phosphorylation
in the mitochondria is running under par (partially blocked) in around half of the ME/CFS patients.
Oxidative phosphorylation I believe is responsible for around 90% of ATP production, so having this process partially blocked may well leave you short of energy. That seems to add up to a pretty straightforward possible explanation for the fatigue felt in ME/CFS.
(The subset of ME/CFS patients whose oxidative phosphorylation is partially blocked they call Group B patients; patients who do not have oxidative phosphorylation problems, with this process running at normal efficiency, they call Group A patents.)
So poor oxidative phosphorylation was one mitochondrial defect that they found in ME/CFS patients.
They also found that the operation of the mitochondrial translocator protein
was often running under par in ME/CFS patients. Since translocator protein is responsible for transporting ATP produced in the mitochondria into the cytosol of the cell (and responsible for transporting ADP back into the mitochondria for recycling), an inefficiency in this process may again leave you short of energy.
So there was more than one way in which mitochondrial energy production was found hampered in ME/CFS patients.
Note that Myhill et al use the term "translocator protein" to refer to the adenine nucleotide translocator (ANT).
Some of the further complexity in the studies comes from the way that ME/CFS patients apparently try to make up for their defective mitochondria and the resulting energy and ATP shortfall:
• Group A patients try to compensate for the mitochondrial ATP shortage by increasing glycolysis to make ATP (glycolysis of course takes place in the cytosol of the cell, rather than the mitochondria);
• Group B patients try to compensate for the shortfall in mitochondrial ATP by another ATP production process; the authors are not entirely sure what this process is in Group B patients, but they think it is most likely the adenylate kinase reaction (which combines two molecules of ADP to make one of ATP and one of AMP).
Source: Myhill 2012
My memory is that the studies were on white cells under laboratory conditions and I doubt you can draw any conclusions about body metabolism from that.
Yes, they use neutrophils to run the lab tests.
But if the major problem in ME/CFS is a dysfunction in the mitochondria themselves, it's possible this will be a global problem found in the mitochondria of most cells; in which case, mightn't a cell like a neutrophil be reasonably representative for all cells?
Myhill et al say this on the issue:
Our experimental results are all obtained from neutrophils. Neutrophils are similar to skeletal muscle cells and most other cells (but not cardiac muscle cells) in that the proton gradient across the mitochondrial inner membrane is about 50 % electrical and 50 % chemical. However, at this stage we cannot claim that the mitochondria in other cell types behave similarly, even though mitochondria are systemic. However, some of the features that we observe are very similar to some of the effects seen in exercise studies of patients with ME/CFS.
Source: Myhill 2012