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Br J Cancer. 2011 Aug 9;105(4):469-74. doi: 10.1038/bjc.2011.245. Epub 2011 Jun 28.

Mitochondrial recoupling: a novel therapeutic strategy for cancer?

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Department of Medicine, VA Boston Healthcare System and Brigham and Women's Hospital, Harvard Medical School, 150 S Huntington Avenue, Room A6-46, Boston, MA 02130, USA.


Recent findings link metabolic transformation of cancer cells to aberrant functions of mitochondrial uncoupling proteins (UCPs). By inducing proton leak, UCPs interfere with mitochondrial synthesis of adenosine 5'-triphosphate, which is also a key determinant of glycolytic pathways. In addition, UCP suppress the generation of superoxide, a byproduct of mitochondrial electron transport and a major source of oxidative stress. The near ubiquitous UCP2 becomes highly abundant in some cancers and may advance metabolic reprogramming, further disrupt tumour suppression, and promote chemoresistance. Here we review current evidence to suggest that inhibition of mitochondrial uncoupling may eliminate these responses and reveal novel anti-cancer strategies.

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