Charlotte Stephens, Research Correspondent, ME Association.
For many years, a leading theory of causation in ME/CFS has been problems with the mitochondria (the part of the cell responsible for generating energy).
However, researchers are now suggesting that this is less likely and that we should be looking for something that is impacting the mitochondria's ability to function properly – rather than at the mitochondria themselves.
In light of this, we have created an overview of mitochondrial research to date; explaining what mitochondria are, exploring the possibility of mitochondrial dysfunction as the cause of ME/CFS and offering other possible explanations if the mitochondria are not to blame.
- Mitochondria are the part of the cell responsible for producing most of the body’s energy.
- Problems with energy production have been found in ME/CFS and have been primarily linked to mitochondrial dysfunction.
- No ‘faulty genes’ or mutations have been discovered in the mitochondria of people with ME/CFS, suggesting it is not a form of classic mitochondrial disease.
- There is conflicting research on the role of mitochondrial function in ME/CFS; some studies have found increased mitochondrial activity, some have found reduced activity, and some have found no differences between ME/CFS and healthy controls.
- Recent research is now indicating that there is a problem with something ‘upstream’ of the mitochondria that is impacting their ability to function i.e. it is not a problem with the mitochondria themselves.
- More research is needed on larger cohorts to identify this upstream factor, but there are already a few theories (and these are discussed in this review).
Mitochondria are small structures inside our cells that generate energy and are often referred to as ‘the powerhouse of the cell’.
They are responsible for converting chemical energy from food into a form that’s readily available for use by the cell, called ATP (adenosine triphosphate).
These energy-rich ATP molecules are the fuel for all of the different functions of the body. Mitochondria allow the cell to produce up to 15x more ATP then they would without them (Davidson, 2015).
Mitochondria are found in every cell in the body, except red blood cells, and there can be up to 2000 mitochondria per cell! There are more of them in parts of the body that use a lot of energy, such as the brain, the heart, the muscles and the liver.
But producing energy is not all these ‘powerhouses’ do; they are also involved in a range of other processes, such as cellular defence mechanisms, immune response signalling, cell signalling, cell growth and cell death (McBride et al., 2006).
ATP (fuel for the cell) is made through the process of ‘cellular respiration’. This is a series of chemical reactions that combines glucose from food with oxygen to make energy.
Water and carbon dioxide are also produced as waste products of this reaction. Special proteins called enzymes are needed to carry out the chemical reactions involved.
Although mitochondria are responsible for around 90% of the cell’s energy production, there are other methods of energy production that the cell can use that don’t require mitochondria.
However, these are a lot less efficient processes that either use a limited fuel supply, produce harmful by-products or are a lot slower.
There are 4 main types of energy production. The first two use glucose as the ‘fuel’ source, whereas the second two use fat and protein:
- Aerobic (requires oxygen). The classic form of respiration that the mitochondria adopt, as described above. It is the main form of energy production the body uses to carry out basic functions and low-intensity activities. On average, 36 molecules of ATP (energy molecules) are produced from 1 molecule of glucose.
- Anaerobic (doesn’t require oxygen). This is what the body switches to during vigorous activity, where your oxygen supply can’t keep up with the energy demand. This reaction produces lactic acid as a by-product, which is harmful and causes muscle fatigue and aching. Only 2 molecules of ATP are produced from 1 molecule of glucose.
- Gluconeogenesis (or fat burning!). This is the slowest form of energy production and can’t be used to supply energy for exercise. The body uses this when glucose is not available and fatty acids become the source of fuel. 1 small fatty acid chain can be used to produce 48 ATP molecules!
- ATP Phosphocreatine (Protein breakdown). This is the quickest, most immediate source of energy, used for short quick bursts, such as sprinting. Lots of ATP are produced from a component of muscle called ‘Creatine phosphate’, until the stores of it run out. This is not a good form of energy to be using often as it breaks down muscle.
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