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Geen afname van


door de mitochondria,

maar een afname

van de mitochondriale omvang

(plus kritiek Booth).






Volgens Smits en kollega's van het Nijmeegs Kenniscentrum Chronische Vermoeidheid

is er bij ME/CVS geen probleem met de produktie va ATP door de mitochondria (energie-fabriekjes), maar een verminderde produktiekapaciteit (net als bij ouderen en inaktieven).


Norman Booth, één van de co-auteurs van de Myhill-mitochondria-studie uit 2009,

(waaruit bleek dat de totale produktieketen beduidend minder energie oplevert voor de cel)

levert via een ingezonden brief aan de redakteur van Mitochondrium (zie onder) kritiek.


Aerobe produktie van ATP (energieproduktie met behulp van zuurstof) kent 4 stappen:

glycolyse, pyruvaat hydrogenase, de citroenzuurcyclus en oxidatieve fosfylering (ETC).


Smits et al. hebben met name gekeken naar de werking van de oxidatieve fosfylering (stap 4).


Volgens Booth zijn er minstens twee zaken die Smits en kollega's over het hoofd zien:

de werking van de citroenzuurcyclus (stap 3), omdat die grondstoffen aanlevert voor stap 4

de transport van grondstoffen (ADP) naar en afvoer van eindprodukten (ATP) uit de "fabriek".










Dear Dr Smits


We have read with great interest your recent article in the Mitochondrion,

"Mitochondrial enzymes discriminate

between mitochondrial disorders and chronic fatigue syndrome".


However, we do not understand why you have not referenced our article

"Chronic fatigue syndrome and mitochondrial dysfunction" [1]

(attached for your convenience)

particularly as you refer to the article by Vermeulen et al [2]

which strongly criticized our article.


We have written a comment to the Vermeulen et al article

(published on-line immediately after the article),

but unfortunately J Transl Med would not allow us to use any figures or tables.


The relevant figures can be seen on the website of Dr David S Bell [3].


It is not our intention to criticise your work,

but to assist in our mutual understanding of

the mechanisms behind chronic fatigue syndrome and

how it's devastating effects on its sufferers might be alleviated.


Some years ago,

one of us (JMH) carried out tests on

the individual complexes of the mitochondrial electron transfer chain

similarly to the way you have done them,

but came to the conclusion that this approach was not very useful.


What is important is the net production of ATP by mitochondria

and its availability for use by the cell in which it is made.


In our studies with neutrophils [1]

we have found that

the concentration of ATP complexed with magnesium

(necessary for usage via the hydrolysis reaction)

for CFS patients is about ½ that of normal controls

but does not correlate with the severity of the illness.


The illness severity is reflected to some extent in

the efficiency of the oxidative phosphorylation process,

but much more dramatically in

how well the inter-transfer of ADP and ATP

between the mitochondria and the cytosol functions.


These features are not revealed in the measurements that you have carried out, and

in this sense our work complements what you have done.


However, we are not completely at ease with

your method of normalising ATP production to CS activity.


This method assumes that ETC production of ATP is independent of CS activity,

and this is not a valid assumption.


The citric acid cycle is a precursor to the ETC and

the latter cannot work without the former.


But the converse is also true.


If the ETC is inhibited for some reason

other than decoupling (where heat is produced instead of ATP),

then pyruvate dehydrogenase and CS activities are inhibited as a result.


It might be very interesting to carry out our ATP profile test

on the other categories of patients that you have tested.



  1. Myhill, S., N.E. Booth, and J. McLaren-Howard, Chronic fatigue syndrome and mitochondrial dysfunction. Int J Clin Exp Med, 2009. 2(1): p. 1-16.
  2. Vermeulen, R., et al., Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity. Journal of Translational Medicine, 2010. 8(1): p. 93.
  3. Bell, D.S. Mitochondrial Dysfunction. Lyndonville News 2011; Volume 8 (1) May: [Available from:]



Mitochondrial enzymes discriminate between mitochondrial disorders and chronic fatigue syndrome.

Mitochondrion 2011. doi:10.1016/j.mito.2011.05.005.

Smits B, Van den Heuvel L, Knoop H, Küsters B, Janssen A, Borme G, Bleijenberg G, Rodenburg B, Van Engelen B.




We studied

the extent of mitochondrial involvement in chronic fatigue syndrome (CFS) and

investigated whether

measurement of mitochondrial respiratory chain complex (RCC) activities

discriminates between CFS and mitochondrial disorders.


Mitochondrial content was decreased in CFS compared to healthy controls,

whereas RCC activities corrected for mitochondrial content were not.


Conversely, mitochondrial content did not discriminate

between CFS and two groups of mitochondrial disorders,

whereas ATP production rate and complex I, III and IV activity did,

all with higher activities in CFS.


We conclude that

the ATP production rate and RCC activities

can reliably discriminate between mitochondrial disorders and CFS.