Metabolic Brain Disease

, Volume 29, Issue 1, pp 19–36 | Cite as

Mitochondrial dysfunctions in Myalgic Encephalomyelitis / chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative and nitrosative stress pathways

  • Gerwyn Morris
  • Michael MaesEmail author
Review Article


Myalgic encephalomyelitis / chronic fatigue syndrome (ME/cfs) is classified by the World Health Organization as a disorder of the central nervous system. ME/cfs is an neuro-immune disorder accompanied by chronic low-grade inflammation, increased levels of oxidative and nitrosative stress (O&NS), O&NS-mediated damage to fatty acids, DNA and proteins, autoimmune reactions directed against neoantigens and brain disorders. Mitochondrial dysfunctions have been found in ME/cfs, e.g. lowered ATP production, impaired oxidative phosphorylation and mitochondrial damage. This paper reviews the pathways that may explain mitochondrial dysfunctions in ME/cfs. Increased levels of pro-inflammatory cytokines, such as interleukin-1 and tumor necrosis factor-α, and elastase, and increased O&NS may inhibit mitochondrial respiration, decrease the activities of the electron transport chain and mitochondrial membrane potential, increase mitochondrial membrane permeability, interfere with ATP production and cause mitochondrial shutdown. The activated O&NS pathways may additionally lead to damage of mitochondrial DNA and membranes thus decreasing membrane fluidity. Lowered levels of antioxidants, zinc and coenzyme Q10, and ω3 polyunsaturated fatty acids in ME/cfs may further aggravate the activated immuno-inflammatory and O&NS pathways. Therefore, it may be concluded that immuno-inflammatory and O&NS pathways may play a role in the mitochondrial dysfunctions and consequently the bioenergetic abnormalities seen in patients with ME/cfs. Defects in ATP production and the electron transport complex, in turn, are associated with an elevated production of superoxide and hydrogen peroxide in mitochondria creating adaptive and synergistic damage. It is argued that mitochondrial dysfunctions, e.g. lowered ATP production, may play a role in the onset of ME/cfs symptoms, e.g. fatigue and post exertional malaise, and may explain in part the central metabolic abnormalities observed in ME/cfs, e.g. glucose hypometabolism and cerebral hypoperfusion.


ME Chronic fatigue syndrome Mitochondria Inflammation Oxidative and nitrosative stress 



Mitochondrial DNA


Reactive oxygen species


Reactive nitrogen species


Nuclear factor κB




Electron transport chain

Coenzyme Q10





Nuclear magnetic resonance


Adenosine diphosphate


Anaerobic threshold


Centers for Disease Control


Fluoro-deoxyglucose positron emission tomography


Magnetic resonance imaging


Single-photon emission computed tomography


Magnetic resonance spectroscopic




Tumor necrosis factor


Oxidative and nitrosative stress


Inducible NO synthase


Polyunsaturated fatty acids




CCAAT-enhancer-binding proteins


B-cell lymphoma 2


Bcl-2-associated X protein




Tumor protein 53


Peroxisome proliferator-activated receptor alpha (


PPAR gamma coactivator








Adenosine monophosphate


Nicotinamide adenine dinucleotide phosphate


T cell receptor



The authors would like to thank Victoria Storey and Arial Gerallt Francis Morris for their secretarial services.

Conflict of interest

The authors do not report conflicts of interests.

Role of funding source

No specific funding was obtained for this specific research.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Tir Na NogLlanelliUK
  2. 2.Department of PsychiatryDeakin UniversityGeelongAustralia
  3. 3.Department of Psychiatry, Phor Por Ror Building, 12th floor, Faculty of MedicineChulalongkorn UniversityBangkokThailand

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