Cell-type specificity, molecular scope and epigenetic basis for mitochondrial and cellular dysfunction in ME/CFS

Principal investigator

Dr Sarah Annesley

Institution

La Trobe University, Melbourne, Australia

Start date

June 2021

Funding

This project is funded by ME Research UK.

Background and aim

Dr Sarah Annesley and Prof. Paul Fisher are based at La Trobe University in Melbourne, Australia. This group’s research interests are focused on the role of the mitochondria in neurological conditions such as Parkinson’s disease, Alzheimer’s disease and ME/CFS.

Found in most cells in the body, mitochondria are small structures whose main role is to convert energy from the food we eat into a form that cells can use, namely molecules called ATP (adenosine triphosphate). For this reason, mitochondria are often referred to as the power plants of the body.

Since a profound lack of energy – a feeling that the muscles are completely drained – is such a common experience of people with ME/CFS, it seems likely that there is something wrong with this complex process of energy storage and production.

Indeed, there is a wealth of research evidence suggesting that the mitochondria are dysfunctional in ME/CFS, and you can read more about this in an article by Dr Eleanor Roberts.

Dr Sarah Annesley

Dr Annesley has found mitochondrial dysfunction in her own research, showing that the final stage of ATP production in the mitochondria was less efficient in ME/CFS cells than in healthy cells. This final stage involves an arrangement of proteins called complex V. The team also found that the activity of TORC1 (an enzyme which regulates this process) was elevated to compensate.

These experiments were conducted in white blood cells called lymphoblasts, which are part of the immune system that protects us from infection and disease. But are these mitochondrial abnormalities also found in other types of cells from people with ME/CFS, which would indicate a more widespread problem?

This is the main question that Dr Annesley hopes to answer in her new study, in which she will determine if these abnormalities in mitochondrial energy production are also present in fibroblasts, which are cells found in the skin. She will also evaluate whether the alterations correlate with the severity of ME/CFS.

In addition, the team will look at whether other cellular pathways are involved, and whether the persistence of these abnormalities is due to epigenetic changes (how specific genes are turned on or off).

A better understanding of mitochondrial dysfunction in ME/CFS may help in the development of diagnostic tests for the disease, and the identification of effective pharmacological treatments.