Schlagwort: mitochondria
Mitochondria and the evolutionary roots of cancer
Cancer is a group of almost 200 diseases that involve variety of changes in cell structure, morphology, and physiology. Cancer phenotype is underlying several alterations in cellular dynamics with three most critical features, which includes self-sufficiency in growth signals and insensitivity to inhibitory signals, evasion of programmed cell death and limitless replicative potential with a potential for the invasion of other organs. Cancer disease is widespread among metazoans. Some properties of cancer cells such as uncontrolled cell proliferation, lack of apoptosis, hypoxia, fermentative metabolism and free cell motility, i.e. metastasis, resemble a prokaryotic lifestyle, which leads to the assumption of a reversal like evolution from eucariotic back to proteobacterial state. This phenotype matches the phenotype of the last universal common ancestor (LUCA) that resulted from the endosymbiosis between archaebacteria and α-proteobacteria, which later became the mitochondria.
A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine
Progressive increase in mtDNA 3243A>G heteroplasmy causes abrupt transcriptional reprogramming
Wallace hypothesized mitochondrial dysfunction as a central role in a wide range of age-related disorders and various forms of cancer. Steadily rising increases in mitochondrial DNA mutations cause abrupt shifts in diseases. Discrete changes in nuclear gene expression in response to small increases in DNA mutant level are analogous to the phase shifts that is well known in physics: As heat is added, the ice abruptly turns to water or with more heat abruptly to steam. Therefore, a quantitative change that is an increasing proportion of mitochondrial DNA mutation results in a qualitative change which coordinate changes in nuclear gene expression together with discrete changes in clinical symptoms.