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AONM Cell Symbiosis Therapy (CST) Series
Mitochondrial Magic
Gilian Crowther MA (Oxon), ND/NT, mBANT, mNNA, CNHC reg, AONM©
Mitochondria are tiny miracle powerhouses sitting in each
of our cells1, producing our energy in the form of ATP –
adenosine triphosphate. On average, every cell has 1,500
mitochondria. Nerve cells have 4,500 to 6,000, and some
have many more2. One billion of them would fit in a grain
of sand, yet, gram for gram, our mitochondria convert
between 10,000 and 50,000 times more energy per second
than the sun3 – Dr. Gottfried Schatz calls them a “Magic
Garden.”4 They make up 10% of our weight overall5 and
around 40% of the weight of our heart6. A resting cortical
neuron requires 4.7 billion moles of ATP per second7. At
least that’s the ideal, in health …
Another vital issue is how our mitochondria are linked to
fatigue. Mitochondria are powered by oxygen, but a huge
number of free radicals are generated in the process.
Mitochondria are the greatest site of reactive oxygen
species in our bodies. The paradox is that while we cannot
exist without oxygen, oxygen is also inherently dangerous
to our existence14. This is because each oxygen atom has
an unpaired electron in its outer valence shell: without
sufficient antioxidants to quench these, they wreak havoc
and produce “oxygen toxicity,” such as the superoxide
anion radical, hydrogen peroxide, and the extremely
reactive hydroxyl radical.
The predecessors of our mitochondria were bacteria,
which is a long story in itself8 – but hugely important when
you consider that this means antibiotics will inevitably
also affect our mitochondria9 – not just our energy, but
everything they regulate. And the spectrum of their
properties is vast. They are essential for the synthesis of
cholesterol10 (vital for lining every blood vessel, nerve
endings, synapses in the brain, all our steroid hormones
…) and heme11 (without which we wouldn’t have
haemoglobin to carry oxygen to our cells, and can’t
detoxify properly, because CYP450, a key detoxification
molecule, has heme at its centre). Fats are ideally burnt
along the beta oxidation pathway, which is in our
mitochondria, so if they are out of action, we can’t
metabolise fats properly. And the ATP they generate has
a signaling function that carries critical messages between
cells, which fails if they are dysfunctional12. They have
even been called “integrator of danger signals”13: evidence
suggests it is the mitochondria that detect danger, and
initiate the body’s “A&E system” – inflammation and
repair.
Why might we lack antioxidants? The poor quality of
much of the soil together with the pesticides, herbicides
and insecticides used to grow our food both deplete it of
nutrients and mean we are ingesting chemicals that are
foreign to our organisms. The incredibly delicate
“batteries” within our mitochondria, called the electron
transport
chain
(https://www.youtube.com/watch?v=xbJ0nbzt5Kw) can
easily fail if the right building blocks are missing, or if
these building blocks cannot reach the mitochondria
because the membrane is blocked. And there are myriad
potential culprits that can block cellular or mitochondrial
membranes. The 80,000 chemicals in commerce – with
thousands of new ones being added each year – surround
us inescapably. The film “Unacceptable Levels” just
released15 documents the many paths these are finding into
our bodies, not to mention the loads we may have been
carrying for years, such as mercury in amalgam fillings.
So the blockage these xenobiotics may be causing is one
thing. Lacking the right nutrients and antioxidants to
power our mitochondria is another. And not everyone’s
detoxification and methylation pathways are working
correctly. Genetic tests will frequently reveal
polymorphisms (deletions) in the genes in these pathways.
Polymorphisms in the coding for enzymes in the
cytochrome P450 system, for example, mean you cannot
metabolise and clear toxins well – whether endogenous
(produced from within your own body), or exogenous
(absorbed from outside), depending on the genes affected.
MTHFR polymorphisms are also hugely important
(C677T or A1298C, whether single or double deletions):
each add their own layer to the puzzle that needs solving16.
Our high-performance ATP generators, the mitochondria,
are therefore often under such pressure that they are forced
to downregulate to prevent cell death. Where do we get
our energy from then? We have “emergency generators”
outside the mitochondria, in the cytoplasm (the gel-like
substance within the cell membrane). Glycolysis in the
cytoplasm produces two moles of ATP for every mole of
glucose. But inside the mitochondria, one mole of glucose
can produce around 36 moles of ATP (and fatty acids
generate even more). Plus we have tens of thousands of
electron transport chains doing this in each mitochondrion
– and often thousands of mitochondria in each cell. So we
have exponentially more energy that can be produced
within our mitochondria when they are functioning
properly compared to just those two per moles of glucose
in the cytoplasm if they are not. Fatigue in mitochondrial
dysfunction is therefore inevitable – one can even see it as
a byproduct of our body’s intelligence, trying to protect
our cells, which might otherwise die. As Dr. Kathleen
Light said at the OFFER 2008 Conference: "Like pain,
fatigue is a vital protective sensory experience…". That
doesn’t help much of course if one is suffering from it –
one wants a remedy! Further AONM posts will discuss
and link to possible avenues to recovery.
The research of Professor Alan Light has also shown that
exertion elevates pro-inflammatory cytokines17. This in
turn causes a drop in mitochondrial membrane potential,
throttling intra-mitochondrial ATP synthesis18. The
reaction is excessive in people with ME. It takes at least
24 to 72 hours for IFN gamma and alpha to be removed
and mitochondrial membrane potential to correct. This
exacerbates the energy depletion already explained. No
wonder post-exertional malaise is so common in those
with ME19.
We saw at the outset how Dr. Gottfried Schatz called the
mitochondria a “Magic Garden.” These intelligent
organelles are always trying to do the best for us,
ultimately, but the results can be a house of horrors if any
one of the factors discussed above goes out of balance long
term. We’ll be discussing further aspects of mitochondrial
dysfunction in later posts.
Endnotes
1. Except for our erythrocytes (red blood cells), which eject their nuclei
and mitochondria when they reach maturity so that they can transfer the
full load of oxygen they are carrying to our cells, rather than using it as
fuel
2. Voet, D., et al (2006). Fundamentals of Biochemistry, 2nd Edition,
John Wiley and Sons, Inc.
3. G. Schatz. The Magic Garden. Annu. Rev. Biochem. 2007. 76:673–
78,
http://www.life.sci.qut.edu.au/epping/LQB381ScROLL/Fronteirs_rev
iews/mitochondria.pdf
4. Op. Cit.
5. Nisoli, E, Carruba, MO. Nitric oxide and mitochondrial biogenesis.
2006. Journal of Cell Science 119, 2855-2862
6. Ruiz-Meana, M, et al. The SR–mitochondria interaction: a new
player in cardiac pathophysiology. Cardiovasc Res (2010) 88 (1): 3039
7. Zhu XH, et al. 2012. Quantitative imaging of energy expenditure in
human brain. Neuroimage 60:2107–2117
8. Gray, MW., Burger, G., Lang BF. (1999 Mar). Mitochondrial
evolution; Zimmer, C. (2009) Science 325, 666 – 668, On the origin of
eukaryotes
9. Duewelhenke, N., et al. (2007). Influence on mitochondria and
cytotoxicity of different antibiotics administered in high concentrations
on primary human osteoblasts and cell lines. Antimicrob Agents .
10. Black, SM, et al, The mitochondrial environment is required for
activity of the cholesterol side-chain cleavage enzyme, cytochrome
P450scc, Proc Natl Acad Sci USA, 1994
11.
Hemoglobin,
Harvard
University
website,
http://sickle.bwh.harvard.edu/hbsynthesis.html
12. Khakh BS, Burnstock G, The double life of ATP. Sci Am. 2009
Dec; 301(6):84-90, 92
13. Tschopp, J. Mitochondria: Sovereign of inflammation? Eur J
Immunol. 2011 May;41(5):1196-202
14. Davies, KJ. Oxidative stress: the paradox of aerobic life Biochem
Soc
Symp.
1995;61:1-31.
http://www.ncbi.nlm.nih.gov/pubmed/8660387
15. http://www.unacceptablelevels.com/
16.
Yasko, A. A Guide to
Nutrigenomic Testing.
http://www.holisticheal.com/media/downloads/guide-tonutrigenomic-testing.pdf
17. White, A.T., Light, A.R., Hughen, R.W., Bateman, L., Martins,
T.B., Hill, H.R., and Light, K.C. (2010) Severity of symptom flare after
moderate exercise is linked to cytokine activity in chronic fatigue
syndrome. Psychophysiology, 1–10
18. Lemaster, JJ, Holmuhamddov, E. Voltage-dependent anion channel
(VDAC) as mitochondrial governator – Thinking outside the box.
Biochim Biophys Acta. 2006 Feb;1762(2):181-90.
19.
Professor
Anthony
Komaroff
http://www.meactionuk.org.uk/documented_pathology_seen_in_mecfs.htm
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