Effects of Deleting Mitochondrial Antioxidant Genes on Life Span

Ünlü, Ercan Selçuk; Koç, Ahmet

doi:10.1196/annals.1395.055

Cited by 61 publications

(50 citation statements)

References 10 publications

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“…Overexpression of SOD 1 in whole lens has been shown to prevent H 2 O 2 -mediated damage in the lens and thus was proposed to help prevent cataract, although this overexpression was not mitochondrial specific . Unlu and Koc, (2007) showed that in yeast, deletion of three genes, SOD1, SOD2, and CCS1 (Copper chaperone for superoxide dismutase), shortened the life span, indicating the potential of these enzymes in the aging process. Mice deficient in SOD 1 have features typical of AMD, older mice exhibited drusen accumulation, thickened Bruch's membrane and choroidal neovascularization (Imamura et al, 2006).…”

Section: Mitochondrial Protective and Repair Systemsmentioning

confidence: 99%

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

Brennan¹,

Kantorow²

2009

Experimental Eye Research

164

141

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Oxidative stress occurs when the level of prooxidants exceeds the level of antioxidants in cells resulting in oxidation of cellular components and consequent loss of cellular function. Oxidative stress is implicated in wide range of age related disorders including Alzheimer's disease, Parkinson's disease amyotrophic lateral sclerosis (ALS), Huntington's disease and the aging process itself (Lin and Beal, 2006). In the anterior segment of the eye, oxidative stress has been linked to lens cataract (Truscott, 2005) and glaucoma (Tezel, 2006) while in the posterior segment of the eye oxidative stress has been associated with macular degeneration (Hollyfield et al., 2008). Key to many oxidative stress conditions are alterations in the efficiency of mitochondrial respiration resulting in superoxide (O 2 -) production. Superoxide production precedes subsequent reactions that form potentially more dangerous reactive oxygen species (ROS) species such as the hydroxyl radical (˙OH), hydrogen peroxide (H 2 O 2 ) and peroxynitrite (OONO -). The major source of ROS in the mitochondria, and in the cell overall, is leakage of electrons from complexes I and III of the electron transport chain. It is estimated that 0.2-2% of oxygen taken up by cells is converted to ROS, through mitochondrial superoxide generation, by the mitochondria (Hansford et al., 1997). Generation of superoxide at complex I and III has been shown to occur at both the matrix side of the inner mitochondrial membrane and the cytosolic side of the membrane (Kakkar and Singh 2007). While exogenous sources of ROS such as UV light, visible light, ionizing radiation, chemotherapeutics, and environmental toxins may contribute to the oxidative milieu, mitochondria are perhaps the most significant contribution to ROS production affecting the aging process. In addition to producing ROS, mitochondria are also a target for ROS which in turn reduces mitochondrial efficiency and leads to the generation of more ROS in a vicious self-destructive cycle. Consequently, the mitochondria have evolved a number of antioxidant and key repair systems to limit the damaging potential of free oxygen radicals and to repair damaged proteins (Figure 1.0). The aging eye appears to be at considerable risk from oxidative stress. This review will outline the potential role of mitochondrial function and redox balance in age-related eye diseases, and detail how the methionine sulfoxide reductase (Msr)

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Section: Mitochondrial Protective and Repair Systemsmentioning

confidence: 99%

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

Brennan¹,

Kantorow²

2009

Experimental Eye Research

164

141

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“…It has been shown that deletion of yeast SOD1, SOD2 and CCS1 genes dramatically decreases the replicative lifespan [14]. In Caenorhabditis elegans, deletion of SOD genes leads to unexpected results; absence of SOD2 gene causes an increase and simultaneous deletion of all five SOD genes causes no shortage in the lifespan [15].…”

Section: Resultsmentioning

confidence: 99%

Absence of superoxide dismutase activity causes nuclear DNA fragmentation during the aging process

Muid

Karakaya

Koç

2014

Biochemical and Biophysical Research Communications

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a b s t r a c tSuperoxide dismutases (SOD) serve as an important antioxidant defense mechanism in aerobic organisms, and deletion of these genes shortens the replicative life span in the budding yeast Saccharomyces cerevisiae. Even though involvement of superoxide dismutase enzymes in ROS scavenging and the aging process has been studied extensively in different organisms, analyses of DNA damages has not been performed for replicatively old superoxide dismutase deficient cells. In this study, we investigated the roles of SOD1, SOD2 and CCS1 genes in preserving genomic integrity in replicatively old yeast cells using the single cell comet assay. We observed that extend of DNA damage was not significantly different among the young cells of wild type, sod1D and sod2D strains. However, ccs1D mutants showed a 60% higher amount of DNA damage in the young stage compared to that of the wild type cells. The aging process increased the DNA damage rates 3-fold in the wild type and more than 5-fold in sod1D, sod2D, and ccs1D mutant cells. Furthermore, ROS levels of these strains showed a similar pattern to their DNA damage contents. Thus, our results confirm that cells accumulate DNA damages during the aging process and reveal that superoxide dismutase enzymes play a substantial role in preserving the genomic integrity in this process.

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“…Mitochondrial antioxidant proteins were identified by using the MitoP2 program [15], in which the mitochondrial target sequence in genes were analyzed and compared with the published experimental data in order to predict the protein localizations with a high accuracy rate [21]. Ten different proteins, Grx2, Ccp1, Sod1, Glo4, Trr2, Trx3, Ccs1, Sod2, Grx5 and Prx1, were found to reside in mitochondria and to have antioxidant properties.…”

Section: Oxidative Stress Tolerancementioning

confidence: 99%

“…Superoxide dismutases (SOD1 and SOD2) and other mitochondrial ROS scavenging enzymes such as thioredoxin (TRX3), thioredoxin reductase (TRR2), peroxiredoxin (PRX1), glutaredoxins (GRX2, GRX5), cytochrome-c peroxidase (CCP1), glyoxalase II (GLO4), and copper chaperone (CCS1) constitute the major mitochondrial defense system against oxidative stress [15]. Among these genes, the role of superoxide dismutases (SOD1 and SOD2) and copper chaperone (CCS1) in both replicative and chronological aging have been studied previously [16,17].…”

Section: Introductionmentioning

confidence: 99%

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Assessment of chronological lifespan dependent molecular damages in yeast lacking mitochondrial antioxidant genes

Demir¹,

Koç²

2010

Biochemical and Biophysical Research Communications

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a b s t r a c tThe free radical theory of aging states that oxidative damage to biomolecules causes aging and that antioxidants neutralize free radicals and thus decelerate aging. Mitochondria produce most of the reactive oxygen species, but at the same time have many antioxidant enzymes providing protection from these oxidants. Expecting that cells without mitochondrial antioxidant genes would accumulate higher levels of oxidative damage and, therefore, will have a shorter lifespan, we analyzed oxidative damages to biomolecules in young and chronologically aged mutants lacking the mitochondrial antioxidant genes: GRX2, CCP1, SOD1, GLO4, TRR2, TRX3, CCS1, SOD2, GRX5, and PRX1. Among these mutants, ccp1D, trx3D, grx5D, prx1D, mutants were sensitive to diamide, and ccs1D and sod2D were sensitive to both diamide and menadione. Most of the mutants were less viable in stationary phase. Chronologically aged cells produced higher amount of superoxide radical and accumulated higher levels of oxidative damages. Even though our results support the findings that old cells harbor higher amount of molecular damages, no significant difference was observed between wild type and mutant cells in terms of their damage content.

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Effects of Deleting Mitochondrial Antioxidant Genes on Life Span

Cited by 61 publications

References 10 publications

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

Absence of superoxide dismutase activity causes nuclear DNA fragmentation during the aging process

Assessment of chronological lifespan dependent molecular damages in yeast lacking mitochondrial antioxidant genes

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