Cause-effect relationships in the mitochondrial energy inefficiency in ME/CFS

Principal investigator

Dr Sarah Annesley

PhD student

Tina Katsaros

Institution

La Trobe University, Melbourne, Australia

Start date

November 2022

Funding

ME Research UK

Background

Dr Annesley is a scientist at La Trobe University in Melbourne, Australia, whose research is focused on the mitochondria, the so-called power plants of the body. These structures are found in every cell in the body, and their role is to convert energy from our food into a form our cells can use, namely molecules called ATP (adenosine triphosphate).

It is therefore no surprise that a significant amount of research into ME/CFS has looked at whether there are abnormalities in the mitochondria and their production of ATP, since this ‘energy currency’ is crucial to normal functioning of the body.

Tina Katsaros and Dr Sarah Annesley

Mitochondrial dysfunction

Much of the research evidence suggests that the mitochondria are indeed dysfunctional in ME/CFS, including previous work from Dr Annesley in which her group identified two specific abnormalities in the final stage of ATP production in the mitochondria.

In white blood cells called lymphoblasts they found that: (1) an enzyme called ATP synthase produced ATP less efficiently in ME/CFS cells than in control cells, and (2) the activity of an enzyme complex called TORC1 (which regulates this process) was increased in ME/CFS cells.

ME Research UK is currently supporting Dr Annesley to investigate this further in other types of cells called fibroblasts. This new PhD project, which will be carried out by Tina Katsaros under the supervision of Dr Annesley, aims to investigate the mitochondrial abnormalities in more detail, and specifically how they interact.

Cause and effect

Tina plans to use a battery of different tests on lymphoblastoid cells from people with ME/CFS and healthy controls, as well as from other patients with genetic mutations known to affect the function of ATP synthase and TORC1. The tests include measurements of mitochondrial respiration, mitochondrial function and TORC1 activity, as well as some genetic and proteomic assessments.

The main questions the team is hoping to answer are whether the previously identified ATP synthase abnormality and/or elevated TORC1 activity cause other cellular abnormalities seen in ME/CFS.

The hope is that their findings will help us understand more about how the mitochondria are affected in people with ME/CFS, and help identify which proteins and processes could be targeted by potential treatments.

Tina completed her honours degree under the supervision of Dr Annesley, studying calcium signalling in Parkinson’s disease. She developed an interest in the ME/CFS research also being conducted in the laboratory, and now has a desire to make a tangible impact in a field affecting so many people.

Leveraging her own passion and expertise, and that of the Annesley laboratory, Tina starts her PhD project with hopes to better understand the cause–effect relationships between energy pathway abnormalities in cells from people with ME/CFS.

ME Research UK is delighted to be able to support Tina’s project and the next stage of her research career.

Tina spoke briefly (c2min) about her research on an Australian radio show called “Einstein A GO-Go” and also highlighted the complexity of ME/CFS, and the delays in the diagnostic process experienced by many people with the disease.

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