Cancer Cell Metabolism: Warburg and Beyond

Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology Department of Biology, Cambridge, MA 02142, USA.
Cell (Impact Factor: 32.24). 10/2008; 134(5):703-7. DOI: 10.1016/j.cell.2008.08.021
Source: PubMed


Described decades ago, the Warburg effect of aerobic glycolysis is a key metabolic hallmark of cancer, yet its significance remains unclear. In this Essay, we re-examine the Warburg effect and establish a framework for understanding its contribution to the altered metabolism of cancer cells.

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    • "Biofilm formation, sporulation or nutrient limitation in prokaryotes are conditions systematically associated with modulation of the OXPHOS outcome [1] [2] [3] [4] [5] [6] [7]. The same is true during eukaryotic cell differentiation or proliferation (see for instance, [8] [9] [10]). "
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    ABSTRACT: Oxidative phosphorylation (OXPHOS) is an essential process for most living organisms mostly sustained by protein complexes embedded in the cell membrane. In order to thrive, cells need to quickly respond to changes in the metabolic demand or in their environment. An overview of the strategies that can be employed by bacterial cells to adjust the OXPHOS outcome is provided. Regulation at the level of gene expression can only provide a means to adjust the OXPHOS outcome to long-term trends in the the environment. In addition, the actual view is that bioenergetic membranes are highly compartmentalized structures. This review discusses what is known about the spatial organization of OXPHOS complexes and the timescales at which they occur. As exemplified with the commensal gut bacterium Escherichia coli, three levels of spatial organization are at play : supercomplexes, membrane microdomains and polar assemblies. This review provides a particular focus on whether dynamic spatial organization can fine-tune the OXPHOS through the definition of specialized functional membrane microdomains. Putative mechanisms responsible for spatio-temporal regulation of the OXPHOS complexes are discussed. This article is part of a Special Issue entitled: Organization and dynamics of bioenergetic systems in bacteria.
    Biochimica et Biophysica Acta (BBA) - Bioenergetics 11/2015; DOI:10.1016/j.bbabio.2015.10.015 · 5.35 Impact Factor
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    • "Many cancer cells dispense completely with ATP generation through the highly efficient mitochondrial respiratory pathway and rely on glycolysis for ATP generation even when growing in the presence of oxygen. This process was originally described in the early part of the last century by Otto Warburg and has since become known as the Warburg effect (Bayley and Devilee, 2012; Hsu and Sabatini, 2008). Though less efficient for energy production, this type of metabolism provides an abundant supply of carbon building blocks necessary for the increased demands of rapidly expanding tissues and tumors (DeBerardinis et al., 2008; Vander Heiden et al., 2009). "
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    ABSTRACT: The transport of pyruvate into mitochondria requires a specific carrier, the mitochondrial pyruvate carrier (MPC). The MPC represents a central node of carbon metabolism, and its activity is likely to play a key role in bioenergetics. Until now, investigation of the MPC activity has been limited. However, the recent molecular identification of the components of the carrier has allowed us to engineer a genetically encoded biosensor and to monitor the activity of the MPC in real time in a cell population or in a single cell. We report that the MPC activity is low in cancer cells, which mainly rely on glycolysis to generate ATP, a characteristic known as the Warburg effect. We show that this low activity can be reversed by increasing the concentration of cytosolic pyruvate, thus increasing oxidative phosphorylation. This biosensor represents a unique tool to investigate carbon metabolism and bioenergetics in various cell types. Copyright © 2015 Elsevier Inc. All rights reserved.
    Molecular cell 08/2015; 59(3):491-501. DOI:10.1016/j.molcel.2015.06.035 · 14.02 Impact Factor
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    • "Aerobic-glycolysis is a unique trait not only of cancer cells but also of the normal immune/stem cells that use this phenomenon to produce intermediary metabolites of glycolysis as the substrates of growth [1] [2]. "
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    ABSTRACT: Reversible decoupling of glycolysis from aerobic-respiration has been widely recognized to be a crucial step in tailoring immune response by the human cells. In this context, the study reported here revealed for the first time that cooperativity between Apoptosis Antagonizing Transcription Factor (AATF) mRNA and miR-2909 within cellular AATF RNome ensures the regulation of mitochondrial uncoupling protein 2 (UCP2) expression in a cyclic fashion and this phenomenon is substantiated when the immune cells face high glucose threat. Copyright © 2015 Elsevier Inc. All rights reserved.
    Blood Cells Molecules and Diseases 06/2015; 55(1):89-93. DOI:10.1016/j.bcmd.2015.05.001 · 2.65 Impact Factor
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