Mitochondrial Metabolic Theory of Cancer
What is cancer?
1. A disease of abnormal or uncontrolled growth? Yes, but how and why?
2. A disease caused by somatic mutations? Well, cancer first or mutations first?
3. A disease caused by mitochondrial metabolic abnormalities induced by chronic non-fatal injury leading to a regressive evolution of affected cells into ancient and undifferentiated cells and each behaving as independent and competitive unicellular organisms within the human body. This we call the Mitochondrial Metabolic Theory of Cancer.
The theory proposes that any number of non-specific influences including age, viral infections, chronic inflammation, intermittent hypoxia, radiation exposure, chemical carcinogens, etc gradually damages mitochondria by disrupting the oxidative phosphorylation process of ATP production.. This leads to the acccummulation of reactive oxygen species and acidification of the micro-environment which further damages both the mitochondria and the nucleus thereby driving somatic mutations. The gradual reduction of oxidative phosphorylation efficiency elicits a mitochondrial stress response through retrograde signalling that activates various oncogenes to upregulate receptors and enzymes in both the glycolysis and the glutaminolysis pathways constituting substrate level (vs oxidative) phosporylation.
Cellular differentiation is a process maintained by the normal functioning of mitochondrial oxidative phosphorylation, so its damage will lead to de-differentiation. This freedom from control will cause cells to enter its default state, marking an evolutionary return back 2.6 billion years back to being unicellular cells in which unbridled proliferation is driven by fermentation metabolism. So, cancer cells are damaged cells which evolved backwards to become independent unicellular organisms competing with neighbouring normal cells for survival instead of co-operating with them as part of a multicellular organism.
