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Heterozygous mutation of Opa1 in Drosophila shortens lifespan mediated through increased reactive oxygen species production.

Tang S, Le PK, Tse S, Wallace DC, Huang T - PLoS ONE (2009)

Bottom Line: We found that heterozygous dOpa1 mutation caused shortened lifespan, increased susceptibility to oxidative stress and elevated production of ROS in the whole Drosophila.Antioxidant treatment partially restored lifespan in the male dOpa1 mutants, but had no effects in the females.Heterozygous dOpa1 mutation is also associated with irregular and dysmorphic mitochondria in the muscle.

View Article: PubMed Central - PubMed

Affiliation: Division of Human Genetics, Department of Pediatrics, University of California Irvine, Irvine, California, United States of America.

ABSTRACT
Optic atrophy 1 (OPA1) is a dynamin-like GTPase located in the inner mitochondrial membrane and mutations in OPA1 are associated with autosomal dominant optic atrophy (DOA). OPA1 plays important roles in mitochondrial fusion, cristae remodeling and apoptosis. Our previous study showed that dOpa1 mutation caused elevated reactive oxygen species (ROS) production and resulted in damage and death of the cone and pigment cells in Drosophila eyes. Since ROS-induced oxidative damage to the cells is one of the primary causes of aging, in this study, we examined the effects of heterozygous dOpa1 mutation on the lifespan. We found that heterozygous dOpa1 mutation caused shortened lifespan, increased susceptibility to oxidative stress and elevated production of ROS in the whole Drosophila. Antioxidant treatment partially restored lifespan in the male dOpa1 mutants, but had no effects in the females. Heterozygous dOpa1 mutation caused an impairment of respiratory chain complex activities, especially complexes II and III, and reversible decreased aconitase activity. Heterozygous dOpa1 mutation is also associated with irregular and dysmorphic mitochondria in the muscle. Our results, for the first time, demonstrate the important role of OPA1 in aging and lifespan, which is most likely mediated through augmented ROS production.

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Related in: MedlinePlus

The shortened lifespan of heterozygous dOpa1 mutants is extendable through the administration of antioxidants in male flies, but not in female flies.dOpa1+/− mutants and dOpa1+/+ controls were transferred to fresh food every two to three days while aging. Male and female dOpa1+/− Drosophila and dOpa1+/+Drosophila were separated and maintained on with and without 100 µM MnTBAP antioxidant food. Longevity assays were performed. MnTBAP feeding significantly extended lifespan of male dOpa1+/− Drosophila (A), but not in the females (B).
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pone-0004492-g004: The shortened lifespan of heterozygous dOpa1 mutants is extendable through the administration of antioxidants in male flies, but not in female flies.dOpa1+/− mutants and dOpa1+/+ controls were transferred to fresh food every two to three days while aging. Male and female dOpa1+/− Drosophila and dOpa1+/+Drosophila were separated and maintained on with and without 100 µM MnTBAP antioxidant food. Longevity assays were performed. MnTBAP feeding significantly extended lifespan of male dOpa1+/− Drosophila (A), but not in the females (B).

Mentions: Exogenously supplemented antioxidant can detoxify ROS and may retard aging. We have shown that antioxidant treatments were able to ameliorate ROS damage-induced glossy eye phenotype in dOpa1 mutant large clones [14]. To study if antioxidant administration can reverse the observed reduced lifespan of the dOpa1+/− mutant strain, we added MnTBAP to the fly food and generated the survival curves for dOpa1+/− flies. Since males and females of the same species may differ in their responses to interventions that affect lifespan [20], we separated male and female flies in the survival study. Indeed we observed sex-specific effects of antioxidant on lifespan in dOpa1+/− flies. While MnTBAP treatment showed no consequences on lifespan of female dOpa1+/− flies, significantly increased lifespan (50% survival time increased by 7 days) was observed in antioxidant-fed male dOpa1+/− flies (Figure 4).


Heterozygous mutation of Opa1 in Drosophila shortens lifespan mediated through increased reactive oxygen species production.

Tang S, Le PK, Tse S, Wallace DC, Huang T - PLoS ONE (2009)

The shortened lifespan of heterozygous dOpa1 mutants is extendable through the administration of antioxidants in male flies, but not in female flies.dOpa1+/− mutants and dOpa1+/+ controls were transferred to fresh food every two to three days while aging. Male and female dOpa1+/− Drosophila and dOpa1+/+Drosophila were separated and maintained on with and without 100 µM MnTBAP antioxidant food. Longevity assays were performed. MnTBAP feeding significantly extended lifespan of male dOpa1+/− Drosophila (A), but not in the females (B).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2637430&req=5

pone-0004492-g004: The shortened lifespan of heterozygous dOpa1 mutants is extendable through the administration of antioxidants in male flies, but not in female flies.dOpa1+/− mutants and dOpa1+/+ controls were transferred to fresh food every two to three days while aging. Male and female dOpa1+/− Drosophila and dOpa1+/+Drosophila were separated and maintained on with and without 100 µM MnTBAP antioxidant food. Longevity assays were performed. MnTBAP feeding significantly extended lifespan of male dOpa1+/− Drosophila (A), but not in the females (B).
Mentions: Exogenously supplemented antioxidant can detoxify ROS and may retard aging. We have shown that antioxidant treatments were able to ameliorate ROS damage-induced glossy eye phenotype in dOpa1 mutant large clones [14]. To study if antioxidant administration can reverse the observed reduced lifespan of the dOpa1+/− mutant strain, we added MnTBAP to the fly food and generated the survival curves for dOpa1+/− flies. Since males and females of the same species may differ in their responses to interventions that affect lifespan [20], we separated male and female flies in the survival study. Indeed we observed sex-specific effects of antioxidant on lifespan in dOpa1+/− flies. While MnTBAP treatment showed no consequences on lifespan of female dOpa1+/− flies, significantly increased lifespan (50% survival time increased by 7 days) was observed in antioxidant-fed male dOpa1+/− flies (Figure 4).

Bottom Line: We found that heterozygous dOpa1 mutation caused shortened lifespan, increased susceptibility to oxidative stress and elevated production of ROS in the whole Drosophila.Antioxidant treatment partially restored lifespan in the male dOpa1 mutants, but had no effects in the females.Heterozygous dOpa1 mutation is also associated with irregular and dysmorphic mitochondria in the muscle.

View Article: PubMed Central - PubMed

Affiliation: Division of Human Genetics, Department of Pediatrics, University of California Irvine, Irvine, California, United States of America.

ABSTRACT
Optic atrophy 1 (OPA1) is a dynamin-like GTPase located in the inner mitochondrial membrane and mutations in OPA1 are associated with autosomal dominant optic atrophy (DOA). OPA1 plays important roles in mitochondrial fusion, cristae remodeling and apoptosis. Our previous study showed that dOpa1 mutation caused elevated reactive oxygen species (ROS) production and resulted in damage and death of the cone and pigment cells in Drosophila eyes. Since ROS-induced oxidative damage to the cells is one of the primary causes of aging, in this study, we examined the effects of heterozygous dOpa1 mutation on the lifespan. We found that heterozygous dOpa1 mutation caused shortened lifespan, increased susceptibility to oxidative stress and elevated production of ROS in the whole Drosophila. Antioxidant treatment partially restored lifespan in the male dOpa1 mutants, but had no effects in the females. Heterozygous dOpa1 mutation caused an impairment of respiratory chain complex activities, especially complexes II and III, and reversible decreased aconitase activity. Heterozygous dOpa1 mutation is also associated with irregular and dysmorphic mitochondria in the muscle. Our results, for the first time, demonstrate the important role of OPA1 in aging and lifespan, which is most likely mediated through augmented ROS production.

Show MeSH
Related in: MedlinePlus