fredag den 26. juli 2019

Complex V is down in ME - does it also explain Electromagnetic Hypersensitivity?

Complex V

Complex V (also known as ATP synthase or F0F1ATPase) is working less efficiently in cells from ME patients (1).


Chemical Intolerance and Electromagnetic Hypersensitivity in ME

ME patients have chemical intolerance (CI), also knowns as multiple chemical sensitivity (MCS). 

I have asked the question:
Complex V is down in ME - does it explain Chemical Intolerance?
http://followmeindenmark.blogspot.com/2019/07/complex-v-is-down-in-me-does-it-explain.html

Several ME patients also have electromagnetic hypersensitivity (EHS). It has been hypothesized that EHS and CI are two etiopathogenic aspects of a unique pathological disorder (2, 3).

Maybe ME, CI and EHS are a unique "Complex V-disease"?


Electromagnetic Fields and Complex V

Humans are exposed to electromagnetic fields (EMFs) from: Radio and television stations and receivers, radar, computers, Wi-Fi antennas, mobile phones, microwave ovens, and many devices used in medicine and industry. Our blood is just under the skin and is exposed to EMFs all the time.

Lassaivia et al have investigated peripheral blood lympho-monocytes exposed to EMFs at 1.8 GHz frequency and 200 V/m electric field strength. Respirometric measurements of mitochondrial activity in intact lympho-monocytes showed:
  • An in increase of the resting oxygen consumption rate after 20 h of exposure, which was coupled to a significant increase of the FoF1-ATP synthase-related oxygen consumption.
  • At lower time-intervals of EMFs exposure (i.e. 5 and 12 h) a large increase of the proton leak-related respiration was observed which, however, recovered at control levels after 20 h exposure.
  • No significant variations in the mitochondrial mass/morphology was observed in EMFs-exposed lympho-monocytes.
  • Altered redox homeostasis was shown in EMFs-exposed lympho-monocytes, which progressed differently in nucleated cellular subsets.

The results suggest the occurrence of adaptive mechanisms put in action, likely via redox signaling, to compensate for early impairments of the oxidative phosphorylation system caused by exposure to EMFs (4).


ME and Complex V

Fisher et al have investigated lymphoblasts from ME patients and found specific mitochondrial respiratory defects and compensatory changes (5).

Respirometry of immortalized ME patient lymphocytes (lymphoblasts) showed:
  • Mitochondrial ATP synthesis by Complex V is inefficient, representing a significantly lower proportion of the basal mitochondrial respiratory activity.
  • Absolute ATP synthesis rates (pmol/min) were not significantly lower than in control cells, while glycolysis rates and steady state ATP levels were unchanged.
  • There was a significant increases in maximum respiratory capacity, including Complex I activity.
  • “Nonmitochondrial” O2 consumption by other cellular enzymes was also elevated. 

The results suggest that ME/CFS cells compensate for the reduced efficiency of ATP synthesis by upregulating mitochondrial respiratory capacity.

The mitochondrial membrane “mass” and genome copy number were unchanged. Thus ME/CFS cells do not have “more” mitochondria, but their mitochondria have greater respiratory capacity. This increased capacity is underutilized because of the Complex V defect, so that the respiratory “spare capacity” was increased and the mitochondrial membrane potential was elevated (5).

I have a new question:
Can continous exposure from electromagnetic fields in the environment put further strain on a compromised complex V in ME patient cells?


A magnetic field is able to influence Complex V

Interestingly, a team of Japanese scientists have succeeded in attaching magnetic beads to the stalks of F1 -ATPase isolated in vitro, which rotated in presence of a rotating magnetic field. F1 -ATPase synthesized ATP from ADP and Pi when rotated in a clockwise direction at a rate of about 5 molecules per second. Additionally, ATP was hydrolyzed when the stalks were rotated in the counterclockwise direction or when they were not rotated at all (6, ref 26 in ref 7).


References

1) Missailidis, D.; Annesley, S.J.; Allan, C.Y.; Sanislav, O.; Lidbury, B.A.; Lewis, D.P.; Fisher, P.R. An isolated Complex V defect and dysregulated mitochondrial function in immortalized lymphocytes from ME/CFS patients. Submitted 2019.

Specific Mitochondrial Respiratory Defects & Compensatory Changes in ME/CFS Patient Cells
https://www.youtube.com/watch?v=SjK39QCPeeY

2) Belpomme DCampagnac CIrigaray P. : Reliable disease biomarkers characterizing and identifying electrohypersensitivity and multiple chemical sensitivity as two etiopathogenic aspects of a unique pathological disorder. Rev Environ Health. 2015;30(4):251-71. doi: 10.1515/reveh-2015-0027. https://www.ncbi.nlm.nih.gov/pubmed/26613326

3) De Luca CThai JCRaskovic DCesareo ECaccamo DTrukhanov AKorkina L   Mediators Inflamm.: Metabolic and genetic screening of electromagnetic hypersensitive subjects as a feasible tool for diagnostics and intervention.  2014;2014:924184. doi: 10.1155/2014/924184. Epub 2014 Apr 9. https://www.ncbi.nlm.nih.gov/pubmed/24812443

4) Lassaivia et al: Exposure to 1.8 GHz electromagnetic fields affects morphology, DNA-related Raman spectra and mitochondrial functions in human lympho-monocytes. PLOS ONE. February 20, 2018.https://doi.org/10.1371/journal.pone.0192894

5) International research symposiym: Mitochondrial function and signalling “Specific mitochondrial respiratory defects and compensatory changes in immortalized ME/CFS patient lymphocytes.” Speaker: Professor Paul Fisher, Latrobe University, VIC, Australia
https://emerge.org.au/wp-content/uploads/2019/03/2019-Symposium-Programme.pdf

6) Itoh et al: Mechanically driven ATP synthesis by F1-ATPase. Nature. 2004 Jan 29;427(6973):465-8. https://www.nature.com/articles/nature02212

7) Neupane et al: ATP Synthase: Structure, Function and Inhibition. De Gruyter 2019.
https://www.degruyter.com/view/j/bmc.2019.10.issue-1/bmc-2019-0001/bmc-2019-0001.xml

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