Monday, May 23, 2016
The degradation of mitochondrial research
Does everyone remember this?
Most especially this bit:
Control is using pyruvate at 5 mmol/l and the ATP synthesis shut down is generated using palmitoyl carnitine at 10 micromol/l. Got that?
Try this one too, plots of pyruvate against palmitoyl carnitine:
And how about this one, increasing doses of palmitoyl carnitine alone, showing self destruction of ATP synthesis with rising doses of palmitoyl carnitine:
Is everyone convinced that allowing anything over, say 5 micromolar palmitoyl carnitine anywhere near a mitochondrion is going to crash ATP synthesis? Lots of experiments, lots of evidence.
Now, this is pretty basic science. What happens when a lab takes their basic science and goes clinical? This is the same lab:
Chronic Reduction of Plasma Free Fatty Acid Improves Mitochondrial Function and Whole-Body Insulin Sensitivity in Obese and Type 2 Diabetic Individuals
Here is the key statement, from the methods:
"Mitochondrial ATP synthesis rate was measured ex vivo with a chemiluminescence technique as previously described (16)".
Reference 16 is the one from which all of the above graphs have been taken. The isolation, washing and feeding of the mitochondria have not been changed. Yet now, in a clinical study showing the wonders of free fatty acid reduction, we get this:
We can ignore the acipimox groups and use the pre treatment open columns. Look at ATP yield from Pyr, this is pyruvate 2.5 mmol/l. Now look at PMC 0.5 and PMC 1. Here we have palmitoyl carnitine being added at either 0.5 mmol/l, ie 500 micromol/l or even 1000 micromol/l, giving comparable rates of ATP synthesis to pyruvate 2.5 mmol/l. That 1000 micromol/l is one hundred times the concentration used in their first paper to shut down electron flow and collapse delta psi.
Where did the inhibition of electron transfer from reduced CoQ to complex III by palmitoyl carnitine go to? What changed?
They went from basic science to a clinical application. Was the basic science correct? Is the clinical paper correct? An interesting set of changes. Makes me thing of the degradation we see so commonly in research, from something which looks sound to something which looks incomprehensible.