Pharmaceutical Research

, 28:2731 | Cite as

Mitochondrial Metabolism Inhibitors for Cancer Therapy

  • Emma E. Ramsay
  • Philip J. Hogg
  • Pierre J. Dilda
Expert Review


Cancer cells catabolise nutrients in a different way than healthy cells. Healthy cells mainly rely on oxidative phosphorylation, while cancer cells employ aerobic glycolysis. Glucose is the main nutrient catabolised by healthy cells, while cancer cells often depend on catabolism of both glucose and glutamine. A key organelle involved in this altered metabolism is mitochondria. Mitochondria coordinate the catabolism of glucose and glutamine across the cancer cell. Targeting mitochondrial metabolism in cancer cells has potential for the treatment of this disease. Perhaps the most promising target is the hexokinase-voltage dependent anion channel-adenine nucleotide translocase complex that spans the outer- and inner-mitochondrial membranes. This complex links glycolysis, oxidative phosphorylation and mitochondrial-mediated apoptosis in cancer cells. This review discusses cancer cell mitochondrial metabolism and the small molecule inhibitors of this metabolism that are in pre-clinical or clinical development.


adenine nucleotide translocase cancer hexokinase metabolism mitochondria 



alpha-tocopheryl succinate


adenine nucleotide translocase


adenosine triphosphate


4-(N-(S-cysteinylacetyl)amino) phenylarsonous acid


flavin adenine dinucleotide


fumarate hydratase


4-(N-(S-cysteinylglycylacetyl)amino) phenylarsonous acid




glucose transporter


glutamate pyruvate transaminase


4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid


hypoxia inducible factor 1


isocitrate dehydrogenase


nicotinamide adenine dinucleotide (reduced)


nicotinamide adenine dinucleotide phosphate (reduced)


non-small-cell lung carcinoma


4-(N-(S-penicillaminylacetyl)amino)phenylarsonous acid


pyruvate dehydrogenase


pyruvate dehydrogenase kinase


succinate dehydrogenase


tricarboxylic acid cycle


voltage dependent anion channel


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Emma E. Ramsay
    • 1
  • Philip J. Hogg
    • 1
  • Pierre J. Dilda
    • 1
  1. 1.Prince of Wales Clinical School, Lowy Cancer Research CentreUniversity of New South WalesSydneyAustralia

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