%0 Journal Article
%T The Mitochondrial Warburg Effect: A Cancer Enigma
%A Hans H. Kim
%A Taeho Kim
%A Euiyong Kim
%A Ji Kyoung Park
%J Interdisciplinary Bio Central
%D 2009
%I IBC
%X "To be, or not to be?¡± This question is not only Hamlet¡¯s agony but also the dilemma of mitochondria in a cancer cell. Cancer cells have a high glycolysis rate even in the presence of oxygen. This feature of cancer cells is known as the Warburg effect, named for the first scientist to observe it, Otto Warburg, who assumed that because of mitochondrial malfunction, cancer cells had to depend on anaerobic glycolysis to generate ATP. It was demonstrated, however, that cancer cells with intact mitochondria also showed evidence of the Warburg effect. Thus, an alternative explanation was proposed: the Warburg effect helps cancer cells harness additional ATP to meet the high energy demand required for their extraordinary growth while providing a basic building block of metabolites for their proliferation. A third view suggests that the Warburg effect is a defense mechanism, protecting cancer cells from the higher than usual oxidative environment in which they survive. Interestingly, the latter view does not conflict with the high-energy production view, as increased glucose metabolism enables cancer cells to produce larger amounts of both antioxidants to fight oxidative stress and ATP and metabolites for growth. The combination of these two different hypotheses may explain the Warburg effect, but critical questions at the mechanistic level remain to be explored. Cancer shows complex and multi-faceted behaviors. Previously, there has been no overall plan or systematic approach to integrate and interpret the complex signaling in cancer cells. A new paradigm of collaboration and a well-designed systemic approach will supply answers to fill the gaps in current cancer knowledge and will accelerate the discovery of the connections behind the Warburg mystery. An integrated understanding of cancer complexity and tumorigenesis is necessary to expand the frontiers of cancer cell biology.
%K Warburg
%K cancer
%K mitochondria
%K high glycolysis
%K pentose phosphate pathway
%K oxidative stress
%K apoptosis
%K ROS
%K altered metabolism
%K signaling pathway
%U http://www.ibc7.org/article/journal_v.php?sid=48