|Jul19-11, 06:02 PM||#1|
Do tumors have functioning mitochondria?
While I have not yet found a satisfactory description of his research methods, I am aware that at the Nobel Prize winning biologist Otto Heinrich Warburg believed at least from 1924 to 1966 that cancer cells generate their ATP primarily from anaerobic metabolism. He was awarded the Nobel Prize in Physiology in 1931.*
If supplied with the same amounts of the same reagents healthy cells use to make ATP, can tumors make as much ATP as healthy cells? What I am wondering is whether tumors' low rate of aerobic metabolism is due to a poverty of supply or an intrinsic inability.
|Jul19-11, 07:07 PM||#2|
Although the Warburg effect is a well established phenomenon, we don't really understand why cancer cells tend to switch to anaerobic metabolism. One reason could very well be a "poverty of supply." Solid tumors, especially before they can recruit new blood vessels through angiogenesis, will often have zones with very low amounts of oxygen. Therefore, in this case, the use of anaerobic metabolism seems to be a simple consequence of the lack of oxygen.
However, cancer cells will still use anaerobic metabolism even if oxygen is plentiful, so a lack of oxygen is not the only reason. The hypothesis that the mitochondria of cancer cell may somehow be damaged could be one explanation. Indeed, the mitochondria are important regulators of programmed cell death (apoptosis), and cancer cells must inactivate apoptosis in order to survive. Perhaps inactivation of apoptosis somehow compromises the ability of the mitochondria to perform aerobic metabolism.
Another hypothesis has to do with thinking about the anabolic pathways (those that build cellular components) as well as the catabolic pathways (those that produce energy) in metabolism. Many of the intermediates produced during glycolysis serve as the starting points for the synthesis of vital cellular components: lipids, amino acids, nucleotides, etc. By shuttling more material through glycolysis, cancer cells may be optimizing their capabilities to build more material at the expense of producing energy less efficiently (see Vander Heiden, Cantley, and Thompson (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324: 1029. doi:10.1126/science.1160809 PMC2849637).
Finally, many cells in early development show "Warburg-like" metabolism, indicating that the metabolic state of cancer cells could merely be an effect of activating the same proliferative signalling pathways that are active in early development.
|cancer, mitochondria, oxygen, respiration, tumors|
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