In Vivo Effects of Methionine Sulfoxide Reductase Deficiency in Drosophila melanogaster.

Kelsey Wilson,Lindsay Bruce,Diana Singkornrat,Kelli Robbins,David Binninger,Lingxi Huang,William Hausman,Katie Foss

doi:10.3390/antiox7110155

Kelsey Wilson, Lindsay Bruce + Show 6 more

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https://doi.org/10.3390/antiox7110155

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Abstract

The deleterious alteration of protein structure and function due to the oxidation of methionine residues has been studied extensively in age-associated neurodegenerative disorders such as Alzheimer’s and Parkinson’s Disease. Methionine sulfoxide reductases (MSR) have three well-characterized biological functions. The most commonly studied function is the reduction of oxidized methionine residues back into functional methionine thus, often restoring biological function to proteins. Previous studies have successfully overexpressed and silenced MSR activity in numerous model organisms correlating its activity to longevity and oxidative stress. In the present study, we have characterized in vivo effects of MSR deficiency in Drosophila. Interestingly, we found no significant phenotype in animals lacking either methionine sulfoxide reductase A (MSRA) or methionine sulfoxide reductase B (MSRB). However, Drosophila lacking any known MSR activity exhibited a prolonged larval third instar development and a shortened lifespan. These data suggest an essential role of MSR in key biological processes.

Highlights

Free radical production is an unavoidable consequence of aerobic respiration and contributes to the aging process as well as certain neurodegenerative diseases.Collectively known as reactive oxygen species (ROS), these potent sources of oxidative stress are primarily produced through cellular respiration in the mitochondria, ROS are produced from various cellular oxidases as well as extracellular sources such as ultraviolet light, radiation and toxins found in the environment
The deletion removes the first three exons, which includes a portion of the open reading frame
There was no significant difference in the duration of the first or second instar or the period from the wandering third instar to eclosion among any of the four genotypes

Summary

Introduction

Free radical production is an unavoidable consequence of aerobic respiration and contributes to the aging process as well as certain neurodegenerative diseases (reviewed in references [1,2,3,4,5,6]).Collectively known as reactive oxygen species (ROS), these potent sources of oxidative stress are primarily produced through cellular respiration in the mitochondria, ROS are produced from various cellular oxidases as well as extracellular sources such as ultraviolet light, radiation and toxins found in the environment. The level of ROS in cells must be carefully regulated, since low levels of ROS can function as signaling molecules that help protect the cells against oxidative damage [9,10,11], whereas excessive amounts can lead to cell death. These protective mechanisms include intracellular antioxidants such as glutathione, enzymes that destroy the ROS before they can do damage, including catalase and superoxide dismutase and mechanisms to repair damage to macromolecules, such as the extensively studied DNA repair systems [8]. More recently there has Antioxidants 2018, 7, 155; doi:10.3390/antiox7110155 www.mdpi.com/journal/antioxidants

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