Astaxanthin extends lifespan via altered biogenesis of the mitochondrial respiratory chain complex III

Astaxanthin is a -carotenoid produced in some bacteria and algae, which has very important industrial applications (i.e., in cosmetics, coloring additive in aquaculture and as a dietary supplement for human). Here, we analyzed the molecular basis of Astaxanthin-mediated prolongevity in the model organism, . The increased lifespan effects of Astaxanthin are restricted in to the adult phase and are uninfluenced by various other carotenoids tested. Genetic analyses indicated that the Astaxanthin-mediated life-extension relies on mitochondria activity, via the Rieske iron-sulfur polypeptide-1 (ISP-1), but is not influenced by the functions of other known longevity-related gene-loci, including , , , or . Biochemical analyses of native respiratory complexes showed that Astaxanthin affects the biogenesis of holo-complex III (and likely supercomplex I+III, as well). Effects on holo-CIII assembly and activity were also indicated by assays, with mitochondria isolated from worms, rodents, human and plants, which were treated with Astaxanthin. These data indicated a cross-species effect on the oxidative phosphorylation (OXPHOS) machinery by the carotenoid, and provide with further insights into the molecular mechanism of animals longevity extension by Astaxanthin.