From ME Research UK: Wiped out. Energy and the mitochondria in ME/CFS

https://www.meresearch.org.uk/wiped-out/

Dr Eleanor Roberts explores the processes by which our body generates energy, and how these may be disrupted in people with ME/CFS.

As anyone with ME/CFS can testify, the reason why people with the illness can’t do many everyday activities with the same ease with which they used to is that their muscles seem drained of energy. But what, in biological terms, is this energy that is so depleted?

Understanding the process by which energy is stored and released in the body, and the ways in which this may be disrupted, could help explain two of the core features of ME/CFS: fatigue and post-exertional malaise.

ATP and the mitochondria

Two of the most important components of energy storage and production in the body are the molecule ATP (adenosine triphosphate), and structures called mitochondria which are found in most cells.

Energy from the food we eat is stored as ATP by a process known as cellular respiration. ATP is often referred to as our energy currency because it can travel around the body and release that energy wherever it is needed.

Found in large numbers in most cells in the body, mitochondria are small structures whose main role is to produce the energy stored within ATP, which is why they are often referred to as the ‘power plants’ of the body.

This whole process of energy storage and production is fairly complicated and involves a variety of other molecules and different biological pathways, so there are lots of ways in which it can go wrong.

One of the challenges in trying to investigate how the mitochondria might be dysfunctional in ME/CFS is narrowing down exactly where any abnormalities might occur.

The structure of mitochondria

Mitochondrial research in ME/CFS

There has been much ME/CFS research in this area, but arriving at a definitive answer is challenging because different studies have used a range of methods to examine the mitochondria in differing cell types, using samples from ME/CFS patients with a variety of levels of function and years of illness, and diagnosed using different criteria.

These factors may have a huge impact on study results, highlighting the unmet need for large, multi-centre investigations using the same protocol and participant criteria to examine one of the basic underlying theories of what causes the disabling symptoms of ME/CFS.

In a bid to rationalise research in this area, Dr Sean Holden and colleagues conducted a systematic review of studies published in English that investigated the mitochondria in adults diagnosed with ME/CFS. In all of these studies, analyses were carried out using validated methods, and the results were compared with those from healthy control subjects.

It should be noted that most of these studies looked at immune cells from the blood, which are easy to access and to work with. But it is not clear whether changes in one cell type will necessarily be reflected in other cell types.

Genetic defects

Although there are currently no signs that people with ME/CFS have any abnormality in the amount of mitochondrial DNA they have, some studies have found differences in mitochondrial DNA haplogroups. These are subgroups of DNA which indicate a common ancestor.

One study reported that people with specific haplogroups were more likely to have experienced particular ME/CFS symptoms, including joint pain, bloating and a “dead/heavy feeling after exercise”.

This suggests that, while haplogroups do not predispose a person to develop ME/CFS, they may play a role in determining which symptoms they experience.

Furthermore, while the DNA itself may be intact, there could be differences in how it is expressed (i.e. what proteins are being made from particular DNA sections). For example, one study of white blood cells found increased expression of genes involved in oxidative stress (which can cause cell damage) and decreased expression of genes involved in metabolism.

Mitochondrial structure

The number and structure of mitochondria in a cell can change according to the needs of the body. One obvious question is whether people with ME/CFS simply have fewer mitochondria available to release energy – but there doesn’t seem to be any evidence of this.

One study has found differences in the structure of mitochondria in ME/CFS patients, namely irregular joining and branching of the cristae. These are folds in the inner membrane of the mitochondria, and are where most of the energy production takes place. So changes in these cristae could conceivably affect energy release. However, other studies have not reported any changes in mitochondrial structure.

Energy production

While the number and structure of mitochondria may not be drastically altered in ME/CFS, there are still lots of ways in which their function and effectiveness can be reduced.

Findings that point to problems in mitochondrial function in ME/CFS include reduced cellular respiration (i.e. the conversion of carbohydrates into ATP) in some cell types, as well as various biochemical abnormalities that may also affect the production of energy as ATP.

These abnormalities involve relatively complex processes, and a more in-depth discussion is beyond the scope of this article (see the links below for more detailed articles).

There is also the possibility that the mitochondria are working fine but the problem lies in a biochemical pathway somewhere else within the cell, and there is a knock-on effect on mitochondrial function.

Summing up

As the energy-producing centres of most cells in the body, the mitochondria seem like the obvious place to look for a cause of the profound fatigue and loss of energy experienced by people with ME/CFS.

There doesn’t yet seem to be a clear picture of what is going on, but research findings to date do strongly suggest some disruption to the mitochondria in ME/CFS. And this may be due more to problems in the actual process of energy production rather than any large genetic or structural faults in the mitochondria.

As this picture becomes clearer, we hope to get closer to understanding what causes the fatigue and post-exertional malaise experienced by people with ME/CFS.

Further reading

If you would like to read more about the function of the mitochondria and how they may be disrupted in ME/CFS, Eleanor has also written articles exploring these areas in greater detail:

Mitochondria – an overview of structure and function

Mitochondria and ME/CFS

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