Question

I keep reading about research into what is called mitochondrial dysfunction in ME/CFS and how this may help to explain why people with ME/CFS have a constantly flat energy battery. So what are mitochondria? And are any of the researchers looking at treatments that could improve mitochondrial function?

Answer

Mitochondria are minute cellular structures called organelles. They have their own genome/genetic material, with a set of 37 genes which are inherited from the maternal side.

They are often called the powerhouses of cells, because they produce about 90% of the energy that cells need to function. This energy is packed into a chemical called ATP – rather like electricity stored in a battery until it’s needed. The more energy that particular cells need, the more mitochondria they have. So cells that need a lot of energy, like muscle cells or nerve cells, may have hundreds or thousands of mitochondria.

Mitochondria also produce signalling molecules that can travel through the bloodstream to control functions throughout the body. So they can influence how nerve cells work and can even start a process to remove damaged cells from the body, a process called apoptosis.

Because mitochondria play such a vital role in so many body processes, researchers now think that they play an important role in the development of many diseases. And this makes mitochondria a target for totally new treatments and strategies aimed at prevention.

In relation to ME/CFS, nerve cells in the brain, spinal cord, and peripheral nervous system use lots of energy. So researchers are exploring whether mitochondria might contribute to various neurological conditions and symptoms, including debilitating fatigue, and might be a good target for treatment.

Clinical trials are now testing whether boosting energy production by mitochondria in the brain can help relieve symptoms of Alzheimer’s disease.

Infections also affect how mitochondria function, and researchers now believe that mitochondrial damage or dysfunction from viruses holds important clues to medical conditions like ME/CFS.

When it comes to research into mitochondrial dysfunction in ME/CFS, back in the early 1980s I used some of my own skeletal muscle in research carried out in Glasgow and Oxford. This demonstrated both structural and functional abnormalities in the mitochondria – the results of the Oxford research being published in The Lancet in 1984.

Since then a considerable number of other research studies have provided further evidence of mitochondrial dysfunction in ME/CFS, and more recently in Long Covid. The MEA has funded Dr Karl Morten to carry mitochondrial research at the University of Oxford.

More recently, a research team at the National Institutes of Health (NIH) in America linked a protein called WASF3 to ME/CFS in one woman. WASF3 is boosted in cells by stress signals from a signalling pathway called the ER stress response pathway. This overproduction disrupts mitochondrial energy production.

Hwang and his colleagues compared muscle tissue samples taken from 14 people with ME/CFS to samples from 10 healthy volunteers. They found substantially higher levels of WASF3 in most of the people with ME/CFS. And in experiments using cells, blocking WASF3 allowed mitochondria to produce energy at normal levels. The researchers are now planning a clinical trial using an FDA-approved drug re-purposed to dampen down ER stress.

So there is a lot of interesting research being carried out into the role of mitochondria in ME/CFS and it’s possible that these findings could provide important leads as to how we can recharge the ME/CFS flat battery.

More Information:

• Mitochondrial function in health and disease from the National Institutes of Health

• Lancet paper: Arnold D, Radda G, Bore P et al. Excessive intracellular acidosis of skeletal muscle in a patient with a post-viral exhaustion/fatigue syndrome