title: Mitochondrial uncoupling in cancer cells: Liabilities and opportunities.
abstract: Acquisition of the endosymbiotic ancestor of mitochondria was a critical event in eukaryote evolution. Mitochondria offered an unparalleled source of metabolic energy through oxidative phosphorylation and allowed the development of multicellular life. However, as molecular oxygen had become the terminal electron acceptor in most eukaryotic cells, the electron transport chain proved to be the largest intracellular source of superoxide, contributing to macromolecular injury, aging, and cancer. Hence, the 'contract of endosymbiosis' represents a compromise between the possibilities and perils of multicellular life. Uncoupling proteins (UCPs), a group of the solute carrier family of transporters, may remove some of the physiologic constraints that link mitochondrial respiration and ATP synthesis by mediating inducible proton leak and limiting oxidative cell injury. This important property makes UCPs an ancient partner in the metabolic adaptation of cancer cells. Efforts are underway to explore the therapeutic opportunities stemming from the intriguing relationship of UCPs and cancer. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux.
authors.affiliation: Department of Medicine, VA Boston Healthcare System and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: gbaffy@bwh.harvard.edu.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Baffy
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D065150:Cellular Reprogramming; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D004357:Drug Synergism; D004734:Energy Metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D000071245:Mitochondrial Uncoupling Proteins / Q000502:physiology*; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013559:Symbiosis; D014475:Uncoupling Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D000071245:Mitochondrial Uncoupling Proteins; D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; D014475:Uncoupling Agents
keywords: Cancer cell; Chemoresistance; Hypoxia-inducible factor; Metabolic flexibility; Mitochondrial respiration; Uncoupling