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A. Carlioz

Bio: A. Carlioz is an academic researcher. The author has contributed to research in topics: Mutant & Superoxide dismutase. The author has an hindex of 1, co-authored 1 publications receiving 749 citations.

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Journal ArticleDOI
TL;DR: It is concluded that the total absence of SOD in E. coli creates a conditional sensitivity to oxygen.
Abstract: Mu transposons carrying the chloramphenicol resistance marker have been inserted into the cloned Escherichia coli genes sodA and sodB coding for manganese superoxide dismutase (MnSOD) and iron superoxide dismutase (FeSOD) respectively, creating mutations and gene fusions. The mutated sodA or sodB genes were introduced into the bacterial chromosome by allelic exchange. The resulting mutants were shown to lack the corresponding SOD by activity measurements and immunoblot analysis. Aerobically, in rich medium, the absence of FeSOD or MnSOD had no major effect on growth or sensitivity to the superoxide generator, paraquat. In minimal medium aerobic growth was not affected, but the sensitivity to paraquat was increased, especially in the sodA mutant. A sodA sodB double mutant completely devoid of SOD was also obtained. It was able to grow aerobically in rich medium, its catalase level was unaffected and it was highly sensitive to paraquat and hydrogen peroxide; the double mutant was unable to grow aerobically on minimal glucose medium. Growth could be restored by removing oxygen, by providing an SOD-overproducing plasmid or by supplementing the medium with the 20 amino acids. It is concluded that the total absence of SOD in E. coli creates a conditional sensitivity to oxygen.

765 citations


Cited by
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Journal ArticleDOI
04 Mar 1993-Nature
TL;DR: Tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O–2 to O2 and H2O2 is reported.
Abstract: Amyotrophic lateral sclerosis (ALS) is a degenerative disorder of motor neurons in the cortex, brainstem and spinal cord. Its cause is unknown and it is uniformly fatal, typically within five years. About 10% of cases are inherited as an autosomal dominant trait, with high penetrance after the sixth decade. In most instances, sporadic and autosomal dominant familial ALS (FALS) are clinically similar. We have previously shown that in some but not all FALS pedigrees the disease is linked to a genetic defect on chromosome 21q (refs 8, 9). Here we report tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O2.- to O2 and H2O2 (ref. 10). Given this linkage and the potential role of free radical toxicity in other neurodenegerative disorders, we investigated SOD1 as a candidate gene in FALS. We identified 11 different SOD1 missense mutations in 13 different FALS families.

6,733 citations

Journal ArticleDOI
TL;DR: This review attempts to present the still-incomplete understanding of how reactive oxygen species are formed inside cells and the mechanisms by which they damage specific target molecules.
Abstract: The phenomenon of oxygen toxicity is universal, but only recently have we begun to understand its basis in molecular terms. Redox enzymes are notoriously nonspecific, transferring electrons to any good acceptor with which they make electronic contact. This poses a problem for aerobic organisms, since molecular oxygen is small enough to penetrate all but the most shielded active sites of redox enzymes. Adventitious electron transfers to oxygen create superoxide and hydrogen peroxide, which are partially reduced species that can oxidize biomolecules with which oxygen itself reacts poorly. This review attempts to present our still-incomplete understanding of how reactive oxygen species are formed inside cells and the mechanisms by which they damage specific target molecules. The vulnerability of cells to oxidation lies at the root of obligate anaerobiosis, spontaneous mutagenesis, and the use of oxidative stress as a biological weapon.

2,023 citations

Journal ArticleDOI
03 Jun 1988-Science
TL;DR: It is proposed that the cell may also decrease such toxicity by diminishing available NAD(P)H and by utilizing oxygen itself to scavenge active free radicals into superoxide, which is then destroyed by superoxide dismutase.
Abstract: A major portion of the toxicity of hydrogen peroxide in Escherichia coli is attributed to DNA damage mediated by a Fenton reaction that generates active forms of hydroxyl radicals from hydrogen peroxide, DNA-bound iron, and a constant source of reducing equivalents. Kinetic peculiarities of DNA damage production by hydrogen peroxide in vivo can be reproduced by including DNA in an in vitro Fenton reaction system in which iron catalyzes the univalent reduction of hydrogen peroxide by the reduced form of nicotinamide adenine dinucleotide (NADH). To minimize the toxicity of oxygen radicals, the cell utilizes scavengers of these radicals and DNA repair enzymes. On the basis of observations with the model system, it is proposed that the cell may also decrease such toxicity by diminishing available NAD(P)H and by utilizing oxygen itself to scavenge active free radicals into superoxide, which is then destroyed by superoxide dismutase.

1,997 citations

Journal ArticleDOI
TL;DR: The different roles of iron in triggering cell death, targets of iron-dependent ROS that mediate cell death and a new form ofIron-dependent cell death termed ferroptosis are described to suggest new therapeutic avenues to treat cancer, organ damage and degenerative disease.
Abstract: The transition metal iron is essential for life, yet potentially toxic iron-catalyzed reactive oxygen species (ROS) are unavoidable in an oxygen-rich environment. Iron and ROS are increasingly recognized as important initiators and mediators of cell death in a variety of organisms and pathological situations. Here, we review recent discoveries regarding the mechanism by which iron and ROS participate in cell death. We describe the different roles of iron in triggering cell death, targets of iron-dependent ROS that mediate cell death and a new form of iron-dependent cell death termed ferroptosis. Recent advances in understanding the role of iron and ROS in cell death offer unexpected surprises and suggest new therapeutic avenues to treat cancer, organ damage and degenerative disease.

1,491 citations

Journal ArticleDOI
TL;DR: Bacteria comprise an exceptionally accessible experimental system that has provided many of the answers to the remaining puzzles in an anaerobic world, and current research seeks to identify these.
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 II appeared, environmental oxygen levels rose very slowly. During this time, microorganisms acquired oxygen tolerance by jettisoning enzymes that use glycyl radicals and exposed low-potential iron-sulfur clusters, which can be directly poisoned by oxygen. They also developed mechanisms to defend themselves against superoxide (O2−) and hydrogen peroxide, partially reduced oxygen species that are generated as inadvertent by-products of aerobic metabolism. 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 many of the answers. This manuscript reviews recent developments and identifies re...

1,379 citations