Mitochondria Primer 3: How It All Goes Terribly Wrong with CancerOctober 08, 2018
References: Mitochondria and Future of Medicine, Nature, Thomas Seyfried on Youtube,
We now know that mitochondria use proton pumps to store potential energy in the form of an electrochemical gradient, and then harnessing that energy as it comes across a membrane to create chemical energy. Every form of life on earth uses this process. Seriously, it's ditto in plants too, just going the other way: storing instead of burning. Instead of being called mitochondria, we call them chloroplasts. Same process. Generate and store energy, in plants' case, from the sun. In every form of animal life on earth, the energy extracted from the electron transport chain is used to move protons across a membrane. It is so universal, pumping protons across a membrane is the central signature of life on Earth.
It is the key, the nexus, the whole kahuna. Complex cells require this to work. It is a miracle. The miracle of complex life on our planet. But not a perfect miracle. This is the model that arose and all life came from. And it has some flaws. Evolution has had several billion years to try and clean those flaws up with different trials and experiments, but some flaws remain.
Here is one example. In order to be extremely flexible to energy demands and flow, mitochondria must have the ability to manufacture their own critical elements. Hence, mitochondria have 5-10 copies of their own DNA still inside them. That allows them to duplicate themselves when there is demand, and increase the number of electron transport chain units (up and down from 10,000 per mitochondria). The vulnerable point is that the DNA is sitting right there next to the sites in the electron transport chain where electrons can escape and damage the DNA. Mitochondrial DNA is surrounded with a puffy coat of proteins like nuclear DNA. Free electrons make "free radicals" that can get in and damage the DNA.
Ok, now we know that the core defect in cancer is that there are broken mitochondrial membranes in every cancer cell. In fact, one could make the argument that cancer is not 500 different diseases but rather broken mitochondria in 500 different tissues. What you see in cancers is that their mitochondrial membranes look like curdled milk instead of ordered arrays of organized membranes. It is not the sole defect, and cancer cells depend on some residual mitochondrial function to live, but it is certainly a signature defect in cancer. And cancer cells can't extract the extent of energy from glucose and fat that a healthy mitochondria can.
Cancer cells depend on the very primitive and limited chopping of glucose in half, to get 2 ATP instead of 38. To fix cancer, to prevent cancer, we have to understand just where in mitochondria that first broken mitochondrial membrane came about. But mitochondria damage remains central to the defect of cancer. What's the core defect? DNA damage in the mitochondria because of electron transport chain proximity to naked DNA. Result: cancer. Cure: reduce the incidence of free electrons escaping. How do you do that? Next week or so.
WWW: What will work for me. I'm determined to master this knowledge base. I know that healthy mitochondria love to run on fat, and injured ones can't use fat at all. Hence, a high-fat diet, or at least a high beta-hydroxy-butyrate diet, helps mitochondria burn fuel smoothly. Where does BHB come from? Vegetables. We know vegetables get turned into beta-HB. We had roasted Morrocan cauliflower for dinner last night.
- What is the key to complex life on planet earth? Answer: The pumping of electrons and protons across membranes and then the miracle of ATP-synthetase, or Complex 4, theworld's smallest machine, that converts electrical energy into chemical energy with a spinning wheel.
- How many sets of mitochondrial DNA are there in a mitochondria? Answer: 5-10
- What is the vulnerability of mitochondrial DNA? Answer: it's naked and close to the production of escaped electrons which form damaging chemicals.
- What is the core defect in cancer? Answer: Broken mitochondria.
- What reduces your risk of cancer? Answer: Running on fat from plants, known as beta-hydroxybutyrate. AKA, more spinach and broccoli.