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

Review Article

Abstract

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.

Keywords

ME Chronic fatigue syndrome Mitochondria Inflammation Oxidative and nitrosative stress 

Abbreviations

mtDNA

Mitochondrial DNA

ROS

Reactive oxygen species

RNS

Reactive nitrogen species

NF-κB

Nuclear factor κB

ATP

Adenosine-5′-triphosphate

ETC

Electron transport chain

Coenzyme Q10

CoQ10

31P

31phosphorous

NMR

Nuclear magnetic resonance

ADP

Adenosine diphosphate

AT

Anaerobic threshold

CDC

Centers for Disease Control

FDG-PET

Fluoro-deoxyglucose positron emission tomography

MRI

Magnetic resonance imaging

SPECT

Single-photon emission computed tomography

MRS

Magnetic resonance spectroscopic

IL

Interleukin

TNF

Tumor necrosis factor

O&NS

Oxidative and nitrosative stress

iNOS

Inducible NO synthase

PUFA

Polyunsaturated fatty acids

CCAAT

Cytidine-cytidine-adenosine-adenosine-thymidine

C/EBPs

CCAAT-enhancer-binding proteins

Bcl-2

B-cell lymphoma 2

Bax

Bcl-2-associated X protein

LPS

Lipopolysaccharides

p53

Tumor protein 53

PPAR

Peroxisome proliferator-activated receptor alpha (

PGC

PPAR gamma coactivator

GSH

Glutathione

MDA

Malondialdehyde

4HN

4-hydroxynonenal

AMP

Adenosine monophosphate

NADPH

Nicotinamide adenine dinucleotide phosphate

TCR

T cell receptor

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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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