Pflügers Archiv - European Journal of Physiology

, Volume 459, Issue 2, pp 269–275 | Cite as

The role of mitochondrial uncoupling proteins in lifespan

  • Marcelo O. Dietrich
  • Tamas L. Horvath
Integrative Physiology


The increased longevity in modern societies raised the attention to biological interventions that could promote a healthy aging. Mitochondria are main organelles involved in the production of adenosine triphosphate (ATP), the energetic substrate for cellular biochemical reactions. The production of ATP occurs through the oxidative phosphorylation of intermediate substrates derived from the breakdown of lipids, sugars, and proteins. This process is coupled to production of oxygen reactive species (ROS) that in excess will have a deleterious role in cellular function. The damage promoted by ROS has been emphasized as one of the main processes involved in senescence. In the last decades, the discovery of specialized proteins in the mitochondrial inner membrane that promote the uncoupling of proton flux (named uncoupling proteins–UCPs) from the ATP synthase shed light on possible mechanisms implicated in the buffering of ROS and consequently in the process of aging. UCPs are responsible for a physiological uncoupling that leads to decrease in ROS production inside the mitochondria. Thus, induction of uncoupling through UCPs could decrease the cellular damage that occurs during aging due to excess of ROS. This review will focus on the evidence supporting these mechanisms.


Aging Mitochondria Free radical Oxidative phosphorylation ATP 



MOD was partially supported by a fellowship from the Conselho Nacional de Pesquisa (CNPq), Brazil.


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Section of Comparative MedicineYale University School of MedicineNew HavenUSA
  2. 2.Programa de Pós-graduação em Bioquímica, Department of BiochemistryUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  3. 3.Departments of Obstetrics, Gynecology and Reproductive SciencesYale University School of MedicineNew HavenUSA
  4. 4.NeurobiologyYale University School of MedicineNew HavenUSA

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