Cellular respiration and dedifferentiation

Abstract

Mitochondria are far more than the powerhouse of the cell as they have classically been described. They are also the location where various catabolic and anabolic processes, calcium fluxes, reactive oxygen and nitrogen species, and numerous signal transduction pathways interact to maintain cell homeostasis and to modulate cellular responses to diverse stimuli. Because of the mitochondrion's vital roles in cell physiology, this organelle squarely falls within the ambit of cancer pathophysiology. Indeed cancer-associated alterations in cell energy metabolism related to mitochondrial dysfunction have been recognized for many years in the so-called Warburg effect. Furthermore, these organelles appear to play a fundamental role in determining whether a cell will undergo cell death by apoptosis or necrosis; and key metabolic enzymes of the tricarboxylic acid (TCA) cycle, the fundamental oxidative pathway of the cell, may act as oncosuppressors. Recent findings indicate that modulation of mitochondrial activities in general, and of its electron respiratory chain in particular, could induce differentiation and/or death of cancer cells. Thus it may be possible to induce anticancer activities by deliberate modulation of cellular respiration. Elucidation of the role of mitochondria in cancer cell dedifferentiation processes may provide a new definition of the dedifferentiation/differentiation of cancer cells as well as important information about the pathophysiology of so-called stem cells, with important diagnostic, prognostic, and therapeutic consequences. © Humana Press, a part of Springer Science+Business Media, LLC 2009.