New aspects of mitochondrial Uncoupling Proteins (UCPs) and their roles in tumorigenesis

Uncoupling proteins (UCPs) belong to a family of mitochondrial carrier proteins that are present in the mitochondrial inner membrane. UCP1 was first identified followed by its two homologs, UCP2 and UCP3. The physiological functions of UCP include lowering mitochondrial membrane potential and dissipating metabolic energy as heat. However, UCP can be dysregulated and may contribute to the pathogenesis of metabolic disorders and obesity. Recent studies suggest that UCP also plays a role in neurodegenerative diseases and atherosclerosis. In addition, the widely expressed UCP, UCP2, has been shown to be upregulated in a number of aggressive human cancers. One mechanism of UCP2 upregulation in these cancers is due to oxidative stress, and elevated UCP2 in turn reduces oxidative stress, which provides a growth advantage for these cancers. Nevertheless, new studies suggest UCP2 may interact with oncogenes and tumor suppressor genes, providing a potential new mechanism of how UCP2 contributes to cancer development. In this review, the evidence supporting the role of UCPs in diseases other than diabetes and obesity, the reports on how UCP is regulated in cancer cells, and how UCP may regulate p53 will be discussed.