The nature and mechanism of superoxide production by the electron transport chain: Its relevance to aging

Abstract

Most biogerontologists agree that oxygen (and nitrogen) free radicals play a major role in the process of aging. The evidence strongly suggests that the electron transport chain, located in the inner mitochondrial membrane, is the major source of reactive oxygen species in animal cells. It has been reported that there exists an inverse correlation between the rate of superoxide/hydrogen peroxide production by mitochondria and the maximum longevity of mammalian species. However, no correlation or most frequently an inverse correlation exists between the amount of antioxidant enzymes and maximum longevity. Although overexpression of the antioxidant enzymes SOD1 and CAT (as well as SOD1 alone) have been successful at extending maximum lifespan in Drosophila, this has not been the case in mice. Several labs have overexpressed SOD1 and failed to see a positive effect on longevity. An explanation for this failure is that there is some level of superoxide damage that is not preventable by SOD, such as that initiated by the hydroperoxyl radical inside the lipid bilayer, and that accumulation of this damage is responsible for aging. I therefore suggest an alternative approach to testing the free radical theory of aging in mammals. Instead of trying to increase the amount of antioxidant enzymes, I suggest using molecular biology/ transgenics to decrease the rate of superoxide production, which in the context of the free radical theory of aging would be expected to increase longevity. This paper aims to summarize what is known about the nature and mechanisms of superoxide production and what genes are involved in controlling the rate of superoxide production.

A detailed morphological, phylogenetic and ecophysiological analysis of four benthic Anabaena (Nostocales, Cyanobacteria) strains confirms deep heterogeneity within the genus

“…Most of the studied strains (04VR10L1, 11VR10JH, and 01DRMII10) showed similar light intensity optima, which were relatively close to those of previously studied planktic species of Dolichospermum (zapomělová et al 2008a (GOns 1997;van liere & mur 1979), the low light intensities employed were apparently insufficient to provide the minimal amount of energy necessary for the growth of Dolichospermum strains studied by Zapomělová et al (2008a). Their death at high light intensities could be explained by oxidative stress and photoinhibition (van liere & mur 1980;herman & d'ari 1998;Muller 2000). In general, planktic strains seem to be adapted to a more homogenous and stable environment without the need for mechanisms to protect against abrupt changes in environmental conditions, whereas the benthic strains investigated in this study presumably possess protective mechanisms that allow them to grow over a wide range of temperatures and light intensities.…”

Protonmotive pathways and mechanisms in the cytochrome bc1 complex

“…In addition, since the quinone and quinol redox reactions involve a semiquinone intermediate, it is advantageous to have these reactions localized to a non-aqueous environment in order to provide a thermodynamic and mechanistic barrier to formation of deleterious oxygen radicals by aberrant reactivities of the semiquinone [3]. Consequently, the linkage of proton chemistry to electron transfer during quinol oxidation at center P and quinone reduction at center N requires mechanisms for moving protons to and from the aqueous phase and the hydrophobic environment in which the quinol and quinone reside.…”

Tissue-specific changes in fatty acid oxidation in hypoxic heart and skeletal muscle

“…Previous reports on rat cardiac tissue indicate that total aconitase protein concentration does not change after 2 wk of hypoxia and propose that it is a posttranslational modification that decreases aconitase activity (15). Hypoxic tissues produce ROS as a result of attenuated electron flow through the ETS when oxygen, the final electron acceptor, is limited (33). In the heart, ROS generation during both acute and chronic hypoxia may therefore inhibit aconitase activity, disrupting TCA cycle flux.…”