Examination of the requirement for ucp-4, a putative homolog of mammalian uncoupling proteins, for stress tolerance and longevity in C-elegans

Reactive oxygen species (ROS) are generated by mitochondrial respiration and can react with and damage cellular components, According to the free radical theory of aging, oxidative damage from mitochondrial ROS is a major cause of cellular decline during aging, Mitochondrial uncoupling proteins (UCPs) uncouple ATP production from electron transport and can be stimulated by free radicals. suggesting UCPs may perform a cytoprotective function. The nematode, Caenorhabditis elegans. contains one UCP-like protein, encoded by the ucp-4 gene. We have investigated the genetic requirement for ucp-4 in normal aging and stress resistance. Consistent with the hypothesis that ucp-4 encodes a putative uncoupling protein, animals lacking ucp-4 function contained elevated ATP levels, However, the absence of ucp-4 function did not affect adult lifespan or survival in the presence of thermal or oxidative stress. Together, these results demonstrate that ucp-4 is a negative regulator of ATP production in C. elegans. but is not required for normal lifespan. Published by Elsevier Ireland Ltd.