Playing Devil's Advocate for a bit, just to show how complicated this is we need to look at the opposite causation in a subset. Say something happens to damage the mitochondria. Then we have an infection that stresses it. The infection essentially reveals the defect by pushing it. Another hypothesis that I found was badly received way back when, but it sometimes discussed now, is the two hit hypothesis, though multiple hit hypothesis is more accurate. It might take multiple factors working together, either simultaneously or sequentially, to trigger the disorder. So for example this might be getting a herpes virus and an enterovirus. What we consider the trigger is the latest one, but what we don't consider is the synergy between the two. You can repeat the two hit hypothesis conjecture with any combination of two factors, or indeed any number of factors. Until the science is done we don't know enough to talk causes without speculating. We can however address results. We can measure abnormalities. Those are the data set that need to be explained. One of the factors I liked in some of Myhill's research was the indication that transfer of critical factors across the mitochondrial membrane was involved. Such transfer is rate limited. So there is NO cranking up the mitochondria. If further damage occurs then transfer can be further inhibited. Something I have always tried to consider is this: mitochondria are essentially not particularly robust bacteria. Antibiotics and other bacterial poisons can in theory hit them hard. So might bacterial phages. I tried to get KDM interested in the phage hypothesis some years ago, but he said they cannot see any mitochondrial infection on investigation. Yet another possibility is the pathogen is not a human pathogen, and does not infect humans. I have considered this from time to time over the years. What if the culprit is a gut bacteria pathogen such as a phage? The gut bacteria are infected, not us, but they will release toxins and other mediating factors, knocking out our immune system and disturbing gut function. I also do not think its a coincidence that nearly all the pathogens known to trigger ME are gut infections and can infect B cells.