Uncoupling proteins: a complex journey to function discovery.
Since their discovery, uncoupling proteins have aroused great interest due to the crucial importance of energy-dissipating system for cellular physiology. The uncoupling effect and the physiological role of UCP1 (the first-described uncoupling protein) are well established. However, the reactions catalyzed by UCP1 homologues (UCPs), and their physiological roles are still under debate, with the literature containing contrasting results. Current hypothesis propose several physiological functions for novel UCPs, such as: (i) attenuation of reactive oxygen species production and protection against oxidative damage, (ii) thermogenic function, although UCPs do not generally seem to affect thermogenesis, UCP3 can be thermogenic under certain conditions, (iii) involvement in fatty acid handling and/or transport, although recent experimental evidence argues against the previously hypothesized role for UCPs in the export of fatty acid anions, (iv) fatty acid hydroperoxide export, although this function, due to the paucity of the experimental evidence, remains hypothetical, (v) Ca(2+) uptake, although results for and against a role in Ca(2+) uptake are still emerging, (vi) a signaling role in pancreatic beta cells, where it attenuates glucose-induced insulin secretion. From the above, it is evident that more research will be needed to establish universally accepted functions for UCPs.
Cioffi
Federica
F
Dipartimento di Scienze della Vita, Seconda Università degli Studi di Napoli, Caserta, Italy.
Senese
Rosalba
R
de Lange
Pieter
P
Goglia
Fernando
F
Lanni
Antonia
A
Lombardi
Assunta
A
D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007473:Ion Channels / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000502:physiology; D024101:Mitochondrial Proteins / Q000502:physiology*; D000071245:Mitochondrial Uncoupling Proteins; D009419:Nerve Tissue Proteins / Q000502:physiology; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D022722:Thermogenesis / Q000502:physiology; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D005227:Fatty Acids; D007328:Insulin; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D000071245:Mitochondrial Uncoupling Proteins; D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species; C116584:SLC25A14 protein, human; C117577:SLC25A27 protein, human; C000604371:UCP1 protein, human; C000604392:UCP3 protein, human; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D005947:Glucose