Premium
Association of C‐terminal region of phosphoglycerate mutase with glycolytic complex regulates energy production in cancer cells
Author(s) -
Kowalski Wojciech,
Nocon Dominika,
Gamian Andrzej,
Kołodziej Jerzy,
Rakus Dariusz
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22998
Subject(s) - phosphoglycerate mutase , glycolysis , mutase , biochemistry , phosphoglycerate kinase , pyruvate kinase , cancer cell , biology , flux (metallurgy) , phosphofructokinase , aldolase a , kinase , anaerobic glycolysis , enzyme , microbiology and biotechnology , chemistry , cancer , genetics , organic chemistry
Cancer cells prefer anaerobic ATP synthesis, regardless of the availability of oxygen. It has been hypothesized that in these cells, glycolytic enzymes associate into a large complex, which results in an increased efficiency of glycolytic flux. However, there is no convincing in vivo evidence supporting this hypothesis. Here, we show that all the enzymes of triose phosphate metabolism, from aldolase to pyruvate kinase consecutively, form a macromolecular complex in vivo and that disruption of such complex significantly inhibits lactate release and ATP synthesis in the glycolytic pathway. Composition of the complex and the effectiveness of the glycolytic flux depends on lactate and glucose concentration. High concentrations of exogenous lactate reduces association of the C‐terminal region phosphoglycerate mutase (PGAM) with the complex which results in its disruption and inhibition of ATP synthesis. Additionally, high lactate affects nuclear localization of PGAM and ceases cell proliferation. Our findings might provide new prospects for cancer treatment using low‐molecular weight competitors to destabilize the glycolytic complex and reduce proliferative potential of cancer cells. J. Cell. Physiol. 227: 2613–2621, 2012. © 2011 Wiley Periodicals, Inc.