MAG-pie & MAG-net Alert…
Iron Toxicity Post #47: The TRUTH about the CAUSE of Mitochondrial Dysfunction… (At least as I see it… )
Over the years, there have been certain phrases that have chaffed me – among the MOST offensive is this term: “Mitochondrial Dysfunction.” It is a term that conjures up an equal amount of fear, wonderment & confusion like that oft used phrase: “Oh, you have a Lesion…” (What the heck does that REALLY mean, anyway?!?…)
And there are THOUSANDS & THOUSANDS of articles, both for the layperson and the scientist, written about this booga-wooga condition that is rapidly becoming a PANDEMIC on this Planet. And when ALL the dust settles, it’s not unlike writing a Magnus Opus about HOW to drive a car — with meticulous detail to EVERY facet of that automotive experience — with the notable exclusion of two KEY & FUNDAMENTAL dimensions to a successful drive:
• Forgetting to tell you that it’s REALLY important to bring a KEY to start the Engine, AND
• Forgetting to tell you that the Engine MUST have Fuel to keep it running… 
Hmmmmmmmmmmm…
Oh, boy… where we headin’ today?!?…
Please take a good LOOOOOONG look at the attached picture. I’ve been looking for this type of picture that DUMBS DOWN the Mitochondrial ETC (Electron Transport Chain) so that I can actually understand it!… And I LOVE that this diagram helps to fill in MANY, MANY blanks that are ubiquitous and cleverly disguised in so much of the scientific Literature…
The Mitochondria are where our ATP (Adenosine Tri-Phosphate) gets made, and ATP are the “packets” of energy that fuel our cellular, tissue, organ & bodily functions. This takes place at Complex IV of the ETC. It’s ridiculously important. And the Mitochondrial Cytochrome proteins, that make up these Complexes, are “the most extensively studied electron-transfer proteins.” WOW!… They must be REALLY important, eh?…
And the Step that should make you sit up and take special notice is called Cytochrome c Oxidase (Complex IV) because it is HERE that 4 electrons get transferred to Oxygen so that H2O can be made and the ATP Molecule can be re-made from ADP. And it turns out that these “Cytochromes” are actually Heme proteins, which means that they contain Ferrous (Fe2+) Iron – the MOST REACTIVE form of Iron, btw – but this CRITICAL Cytochrome c Oxidase enzyme does NOT work without Bioavailable Copper.
AGAIN, here is the KEY to make the ATP-Engine work!
And who is supplying the “Copper energy” for this critical aspect of our metabolism?… None other than Ceruloplasmin! For those seeking added mineral insight into this metabolic dynamic, please read Broderius, 2010: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854028/pdf/nihms-192848.pdf
Please also note that there’s Oxidative Stress being given off on BOTH sides of this Mitochondrial process. Oxidative Stress is a natural byproduct of these activities, and it turns out the GREATEST source of endogenous Oxidative Stress occurs across these CRITICAL Mitochondrial actions of Complex I thru V.
But please keep in mind that we’re being trained – like Circus Bears – to think that ONLY Cu/Zn-SOD (SOD I) works the intracellular space (i.e. outside the Mitochondria…) and that ONLY Mn-SOD (SOD II) works the Intra-Mitochondrial Membrane. And I used to think that was the case, too, UNTIL I found this “ancient” blockbuster pf an article on Ceruloplasmin… (Goldstein, 1979):
http://www.jbc.org/content/254/10/4040.full.pdf
What’s notable about the Ceruloplasmin Ferroxidase enzyme is that it is a recognized “Scavenger of Superoxide Radicals” – those are the reactive Oxygen (*O2-) molecules that are quite destructive, but as you can see from the Diagram below, they can & do devolve – both INSIDE & OUTSIDE the Mitochondria — into the MOST DESTRUCTIVE molecule in the body, OH-, which is known as the Hydroxyl Radical. (That my fellow MAG-pies & MAG-nets is what *Dings* DNA to create Epi-genetic CHAOS to support MTHFR…)
It is ALSO what leads to a breakdown in the efficiency & impact of the energy production of these Mitochondria, aka Chronic Fatigue Syndrome, and a host of other chronic conditions of LOW energy.
It is ALSO what disrupts the cellular machinery of our Livers, our Hearts, our Brains, our Kidneys, our Joints, our Muscles… Are you all beginning to see why this thing “Mitochondrial Dysfunction” is such a BIG deal… And some cells have as many as 200-500 Mitochondria in them… But it is NOT nearly as complicated as it’s being methodically made out to be, imho.
Furthermore, what I was NOT certain about — until today — is that Ceruloplasmin is NOT just restricted to the Cytoplasm, i.e. OUTSIDE the Mitochondria. It turns out that this “Scavenger” is, FOR A FACT, found INSIDE the Mitochondria, as well. At least it is WELL-DOCUMENTED in Russian research!… 😉
https://www.ncbi.nlm.nih.gov/m/pubmed/15773547/
https://www.ncbi.nlm.nih.gov/m/pubmed/1232838/ (I have learned over the years to regard the Abstracts that have NO Abstract as being REALLY important…)
So the Plot begins to thicken with the benefit of these penetrating insights ^^^^…
And here’s the BLOCKBUSTER, at least I think it is…
It turns out that 20% of the Mitochondrial Bi-Lipid Membrane is made up of a phospholipid called “Cardiolipin.” And while it’s 20% of the total composition, it’s actually 50% of the phospholipids found to be a part of the Electron Transport Chain (i.e. Complexes I – V) lipids. Here’s the article that offers KEEN insight to the dynamics between Cardiolipin and Superoxide…https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1136634/pdf/biochemj00192-0227.pdf
It turns out that Cardiolipin is ESSENTIAL for the function of Cytochrome c Oxidase. WOW!… I’ve read scores of articles on this Complex IV enzyme, Cytochrome c Oxidase, but I’ve NEVER read that before! And their interaction is “electrostatic” in nature, as I’m sure EVERYTHING is that happens in our bodies… (More on that in a future Post… )
So what does this mean?
• Copper is the KEY to start this Cytochrome c Oxidase Enzyme production of ATP…
• Cardiolipin is the FUEL upon which the Cytochrome c Oxidase Enzyme works…
And what do the PROs from Dover have to say about the ORIGIN of Mitochondrial dysfunction:
“Mitochondrial dysfunction… is related to a decreased Cytochrome c Oxidase activity, ultimately because of Cardiolipin peroxidation [aka, rusting of the fats…] (Smith et al, 1980; Okayasu et al, 1985) CAUSING [emphasis added] a diminished Cytochrome c binding to this enzyme.”
(In High School mathematics, we used to write Q.E.D. which is Latin for Quid Est Demonstratum, which when translated: “It is proven…”)
And in the absence or the presence of lowered production of Ceruloplasmin (which is QUITE common around the Globe, mind you), those ubiquitous Superoxide (*O2-) molecules get FURTHERED “radicalized” – by FERROUS (Fe2+) Iron – into the OH- radical that THEN OXIDIZES THE CARDIOLIPIN…
Call me crazy, but I happen to think it is relevant and MOST VITAL that Ceruloplasmin brings BOTH the Copper KEY AND ensures that the Cardiolipin (FUEL) does NOT get rusty!… not to mention the fact that Ceruloplasmin, as the Ferroxidase enzyme, converts Ferrous (Fe2+) Iron into Ferric (3+) Iron, the latter form of Iron being what can then be used in cellular transport and other metabolic proteins to keep us healthy & energized. WOW!… It does ALL of that?!? (And even MORE!… 😉 )
So, please do NOT be thrown off by this term: Mitochondrial dysfunction. It is a critical issue, as we ALL recognize & know, but it can be whittled down to size and made far easier to understand, as well as to comprehend, once we understand HOW we can prevent or reverse its development in our metabolism.
Again, it is NOT a Medical Disease. Mitochondrial Dysfunction is simply a clinical sign of Mineral Dysregulation – pure & simple…
And for those seeking direction on what to do to address this, please go here to get started:
http://gotmag.org/the-root-cause-protocol/
A votre sante!
MORLEY M. ROBBINS
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