The International Journal of Biochemistry & Cell Biology
Mini-reviewThe mitochondrial uncoupling protein-2: current status
Section snippets
UCP2: a new member of the mitochondrial carriers
Mitchell's chemio-osmotic theory requires a coupling between electron transport by the respiratory chain (respiration) and ATP synthesis (phosphorylation) at the mitochondrial level. However, the mitochondrial coupling of oxygen consumption to ADP phosphorylation is only partial in most cells. The impermeability of protons to the inner mitochondrial membrane appears to be an essential component of the coupling (Fig. 1). Nevertheless the mechanisms involved in modifying proton conductance of the
Tissue distribution in human and rodents
In contrast to the specific localisation of UCP1 in BAT, and UCP3 in skeletal muscle, heart and BAT, UCP2 has a nearly ubiquitous pattern of expression [29], [31]. Fig. 6 shows the pattern of mRNA expression of the different members of the UCP family in rodents.
Regulation of UCP2 expression (see Table 1)
Unlike UCP1, no reliable specific anti-UCP2 antibody is currently available and all the studies of regulation of UCP2 expression are based on the measurement of mRNA levels. Several molecules and various physiological situations involved in the control of energy balance, have been studied for their influence on UCP2 expression.
UCP2 in obesity and diabetes
Since UCP2 may play a role in energy dissipation, several groups have studied its regulation in mouse and human obesity and diabetes, situations with altered energy homeostasis. That UCP2 regulation may be relevant to the physiology of obesity was first suggested by the observation that message levels increased in several mice strains fed on a high fat diet [29]. In several models of animal obesity, the level of UCP2 mRNA is increased in comparison with lean controls [31], but this is not
Directions for future research
A role for UCP2 in the fever response to infection seems plausible and could allow a better understanding of the molecular mechanisms controlling fever. Indeed, Faggioni et al. [28] administered lipopolysaccharids (LPS) to mice and observed an increase of body temperature (fever) and of the UCP2 mRNA level in liver. Indomethacin, an antipyretic drug reversed these effects. This field of investigation seems attractive and a putative role of UCP2 in the cells of the immune system, especially in
Acknowledgements
CF was supported by a Ph.D. thesis fellowship of the Direction des Recherches, Etudes et Techniques and by Institut Danone, DS is owner of a ‘Human Mobility Program’ grant from the European Union Research. The laboratory was supported by the Centre National de la Recherche Scientifique, the Association pour la Recherche contre le Cancer, AFM and Laboratoires Servier. We thank Dr Daniel Ricquier, Dr Bruno Miroux, Dr Ian Colison and Dr Roger Karess for reading the manuscript and Dr Marta Llovera
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