In recent years there has been renewed interest and focus on mitochondria of animal and human tissues. This interest commenced in the latter part of the past century and has gained momentum during the first eight years of this new millennium. The well accepted reason is that mitochondria are now recognized to represent not only "power houses", i.e., the
ATP production factories of tissues essential for cell life, but in response to a variety of different "cues" may participate significantly also in cell death, both that associated with normal turnover and that associated with disease. Conversely, in
cancers (particularly the advanced) their mitochondria interact with
hexokinase 2 (HK-2) resulting in suppression of cell death while supporting cell growth via enhanced glycolysis, even in the presence of
oxygen (Warburg effect). The identification/elucidation of
proteins and mechanisms involved in deciding and/or participating in cell fate (i.e., life, death, or
cancer) has focused to a large extent on the mitochondrial outer compartment, which is taken here to collectively include the outer membrane, the space between the inner and outer membranes, and contact regions between these two membranes. Among the established
proteins believed to be involved in events related to cell fate are "VDACs" that form the basis of this mini-review series. This brief introductory review focuses mainly on the past discovery by the author and colleagues that VDAC located within the outer mitochondrial compartment and its binding partner HK-2 are pivotal players in the "Warburg effect" in
cancer. As one case in point, when
glucose is added to liver cytosol (mitochondria-free) the rate of glycolysis is very low. However, upon addition of
tumor mitochondria containing VDAC bound HK-2, the low glycolytic rate is increased to a high rate near that catalyzed by the
tumor cytoplasm from which the
tumor mitochondria were derived.