Mitochondria are involved with a multitude of processes in our cells and the more we’ve uncovered, the more they seem to do. Perhaps the most well known theory of cancer is the somatic mutation theory – that DNA mutations primarily trigger oncogenesis. Whilst this may well be the case, more evidence has emerged that mitochondrial activity can facilitate cancer alone, and that metabolic conditions caused by failing cellular batteries might in fact initiate it and cause cancerous behaviour.
Nobel laureate Otto Warburg postulated the theory that cancer might be formed by metabolic changes through the ‘Warburg Effect’; cancer cells by and large seem to produce energy through a higher rate of glycolysis followed by lactic acid fermentation, in contrast to normal cells which display lower glycolysis along with oxidation of pyruvate in mitochondria (oxidative phosphorylation, or OXPHOS). This difference was initially suggested to be a cause, but many believed it was simply a symptom caused by genetic mutations. Which exactly triggers the other has been a contentious issue, but as evidence has emerged that mitochondria can both effect genomic stability and be affected by it, a recent review suggests it may often be a failure of OXPHOS which causes genomic changes ending in cancer.
When researchers from the University of Pennsylvania silenced a critical enzyme in oxidative phosphorylation to test this hypothesis further, the affected cells exhibited many of the same behaviours as cancerous populations do, including a lack of contact inhibition and invasive behaviour. Disrupting mitochondria activity also had a knock on effect on the nucleus, triggering:
‘The mitochondria to activate a stress signal to the nucleus, akin to an “SOS” alerting the cell that something is amiss. Avadhani and his colleagues had previously seen a similar pathway activated in cells with depleted mitochondrial DNA, which is also linked to cancer’
Cancer and metabolism are both immensely complicated processes and although it’s unlikely there is one, elegant reason for cancer formation, faulty mitochondrial activity appears to be linked to tumorigenesis and may indeed be a key factor in forming more aggressive cancers as well.
Read more at Medical Express
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