The role of mitochondrial uncoupling proteins in lifespan.
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.
Dietrich
Marcelo O
MO
Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Horvath
Tamas L
TL
D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D004579:Electron Transport / Q000502:physiology; D004734:Energy Metabolism; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D008136:Longevity / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000502:physiology*; D025261:Mitochondrial Proton-Translocating ATPases / Q000502:physiology; D010085:Oxidative Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D000071256:Uncoupling Protein 1
D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D000071256:Uncoupling Protein 1; D013481:Superoxides; D000255:Adenosine Triphosphate; D025261:Mitochondrial Proton-Translocating ATPases