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…

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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…

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Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci

Daniel Smeets, Yolanda Markaki, Volker J Schmid, Felix Kraus, Anna Tattermusch, Andrea Cerase, Michael Sterr, Susanne Fiedler, Justin Demmerle, Jens Popken, Heinrich Leonhardt, Neil Brockdorff, Thomas Cremer1, Lothar Schermelleh and Marion Cremer Abstract Background A Xist RNA decorated Barr body is the structural hallmark of the compacted inactive X territory in female mammals. Using super-resolution three-dimensional structured illumination microscopy (3D-SIM) and quantitative image analysis, we compared its ultrastructure with active chromosome territories (CTs) in human and mouse somatic cells, and explored the spatio-temporal process of Barr body formation at onset of inactivation in early differentiating mouse embryonic stem cells (ESCs)….

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