Voltage dependent anion channels (VDACs): A brief introduction with a focus on the outer mitochondrial compartment's roles together with hexokinase-2 in the "Warburg effect" in cancer

Peter L Pedersen

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)123-126
Number of pages4
JournalJournal of Bioenergetics and Biomembranes
Volume40
Issue number3
DOIs
StatePublished - Jun 2008

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Voltage-Dependent Anion Channels
Hexokinase
Mitochondria
Neoplasms
Glycolysis
Membranes
Cell Death
Liver Mitochondrion
Cytosol
Cues
Cytoplasm
Proteins
Adenosine Triphosphate
Oxygen
Glucose
Growth

Keywords

  • Cancer
  • Glycolysis
  • Hexokinase-2
  • Mitochondria
  • VDAC
  • Warburg effect

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

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title = "Voltage dependent anion channels (VDACs): A brief introduction with a focus on the outer mitochondrial compartment's roles together with hexokinase-2 in the {"}Warburg effect{"} in cancer",
abstract = "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.",
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