New data on biochemical mechanism of programmed senescence of organisms and antioxidant defense of mitochondria.
Much evidence has recently been reported suggesting that reactive oxygen species (ROS) produced in mitochondria play a crucial role in the programmed senescence of organisms. In particular, it has been shown that antioxidants addressed to mitochondria slow down the appearance of symptoms of senescence and development of senile diseases and increase the median lifespan of various organisms from fungi to mammals. At the biochemical level, the mechanism of action of such rechargeable antioxidants as plastoquinonyldecyltriphenyl phosphonium (SkQ1) includes, in particular, prevention of oxidation of mitochondrial cardiolipin by ROS. The hormone melatonin also exhibits a number of such effects, and decrease in its level with age could explain the weakening of antioxidant protection upon aging. According to Moosmann et al., there exists a natural mechanism of antioxidant protection that, like SkQ1, is localized in the internal mitochondrial membrane and is rechargeable. It involves methionine residues in the surface regions of proteins encoded by mitochondrial DNA. It appears that in organisms with high respiratory metabolism the genetic code in the mitochondrial system of protein biosynthesis has changed. In these organisms (including some yeasts, insects, crustaceans, and vertebrates), the AUA codon codes for methionine rather than isoleucine, as in the case of synthesis of proteins encoded either in the nucleus or in mitochondria of organisms with lower rates of metabolism (other yeast species, sponges, and echinoderms). Methionine quenches ROS, being converted to methionine sulfoxide, which is re-reduced to the initial methionine by NADPH.
Skulachev
V P
VP
Belozersky Institute of Physico-Chemical Biology and Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, 119991, Russia. skulach@belozersky.msu.ru
D000375:Aging; D000975:Antioxidants / Q000378:metabolism*; D008550:Melatonin / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species; D008550:Melatonin