Superoxide dismutase evolution and life span regulation.
Superoxide is among the most abundant reactive oxygen species (ROS) produced by the mitochondria, and is involved in cellular signaling pathways. Superoxide and other ROS can damage cellular macromolecules and levels of oxidative damage products are positively correlated with aging. Superoxide dismutase (SOD) enzymes catalyze the breakdown of superoxide into hydrogen peroxide and water and are therefore central regulators of ROS levels. Genetic and transgenic manipulation of SOD activities in model systems such as S. cereviseae, mouse and Drosophila are consistent with a central role for SOD enzymes in regulating oxidative stress resistance. Over-expression of SOD in S. cereviseae and Drosophila can reduce oxidative damage and extend life span, but the mechanism(s) are not yet clear. A phylogenetic analysis of publicly available SOD protein sequences suggests several additional conserved gene families. For example, in addition to the well-characterized soluble Cu/Zn enzyme (Sod) and mitochondrial manganese-containing form (Sod2), Drosophila melanogaster is found to contain a putative copper chaperone (CCS), an extracellular Cu/Zn enzyme (Sod3), and an extracellular protein distantly related to the Cu/Zn forms (Sodq). C. elegans and blue crab are unusual in having two Mn-containing SODs, and A. gambiae contains an unusual internally repeated SOD. The most parsimonius conclusion from the analysis of the extracellular SODs is that they evolved independently multiple times by addition of a signal peptide to cytoplasmic SOD.
Landis
Gary N
GN
Molecular and Computational Biology Program, Department of Biological Sciences, SHS172, University of Southern California, Los Angeles, CA 90089-1340, USA.
Tower
John
J
D000818:Animals; D019143:Evolution, Molecular; D006801:Humans; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D010802:Phylogeny; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D013482:Superoxide Dismutase