title: Mitochondrial recoupling: a novel therapeutic strategy for cancer?
abstract: 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.
authors.affiliation: 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. gbaffy@partners.org
authors.forename: G
authors.initials: G
authors.lastname: Baffy
authors.forename: Z
authors.initials: Z
authors.lastname: Derdak
authors.forename: S C
authors.initials: SC
authors.lastname: Robson
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006019:Glycolysis; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014475:Uncoupling Agents / Q000378:metabolism / Q000494:pharmacology; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2
chemical_list: D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D016159:Tumor Suppressor Protein p53; C000604389:UCP2 protein, human; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D013481:Superoxides; D000255:Adenosine Triphosphate