Cellular Defenses against Superoxide and Hydrogen Peroxide

Abstract

Life evolved in an anaerobic world; therefore, fundamental enzymatic mechanisms and biochemical pathways were refined and integrated into metabolism in the absence of any selective pressure to avoid reactivity with oxygen. After photosystem 2 appeared, environmental oxygen levels rose very slowly. During this time microorganisms acquired oxygen tolerance by jettisoning enzymes that use glycyl radicals and low-potential iron-sulfur clusters, which can be directly poisoned by oxygen. They also developed mechanisms to defend themselves against O 2 − and hydrogen peroxide, partially reduced oxygen species that are generated as inadvertent by-products of aerobic metabolism. These species are more chemically reactive than is molecular oxygen itself. Contemporary organisms have inherited both the vulnerabilities and the defenses of these ancestral microbes. Current research seeks to identify these, and bacteria comprise an exceptionally accessible experimental system that has provided the many of the answers. This manuscript reviews recent developments and identifies remaining puzzles.

Genomic island genes in a coastal marine Synechococcus strain confer enhanced tolerance to copper and oxidative stress

“…Sync_1495 was chosen because it is the longer of the two genes, which makes it a more feasible target for eventual genetic inactivation, which is discussed below. In quantitative reverse transcription-PCR (QRTPCR) experiments sync_1495 was also significantly induced by methyl viologen (Figure 1b), which is a mild oxidant that subsequently reduces oxygen and generates superoxide anions (Imlay, 2008). The gene was not induced by AlexaFluor-488 C 5 maleimide, which binds to surface free thiols, and in microarray experiments (S Tetu, D Johnson, K Phillippy, R Stuart, C Dupont, K Hassan, B Palenik and I Paulsen, unpublished data), the gene was also not significantly induced by ethidium bromide, mitomycin C, or salt shock (Figure 1b).…”

Peroxide‐Sensing Transcriptional Regulators in Bacteria

“…The expression of iron-binding proteins, like Dps, is often induced in response to oxidative stress to reduce the levels of free Fe in order to prevent production of • OH via the Fenton reaction (12). Strategies are also employed to protect enzymes that contain vulnerable Fe-containing centers from oxidation by increasing the uptake of Mn 2ϩ , which is able to replace Fe 2ϩ at some active sites, rendering them resistant to oxidation (50). In some cases, Fe-containing enzymes are replaced with analogs that do not require Fe (70).…”

Intermolecular electron transfer in two-iron superoxide reductase: a putative role for the desulforedoxin center as an electron donor to the iron active site

“…Oxidative stress represents one of the major challenges that organisms living in contact with oxygen have to face [1,2]. It corresponds to the formation of reactive oxygen species (ROS) during aerobic metabolisms, such as superoxide radical (O 2 •-), hydrogen peroxide (H 2 O 2 ) and the hydroxyl radical (HO • ), which are highly toxic for cells.…”

“…It corresponds to the formation of reactive oxygen species (ROS) during aerobic metabolisms, such as superoxide radical (O 2 •-), hydrogen peroxide (H 2 O 2 ) and the hydroxyl radical (HO • ), which are highly toxic for cells. Cells express very efficient antioxidant systems which detoxify these species [1,2]. In the case of the superoxide radical, only two classes of enzymes able to detoxify it have been described: the superoxide dismutase (SOD) [3], expressed in almost all cells living in contact with oxygen, and the more recently discovered superoxide reductase (SOR) which has been found in some microaerophilic and anaerobic bacteria [4][5][6][7][8][9].…”