Expression of the methionine sulfoxide reductase lost during evolution extends Drosophila lifespan in a methionine-dependent manner

Byung Cheon Lee,Andrei S Avanesov,Hae Min Lee,Vadim N Gladyshev,Sorah Kim,Aro Lee,Bok-Hwan Chun,Gerd Vorbruggen

doi:10.1038/s41598-017-15090-5

Byung Cheon Lee, Andrei S Avanesov + Show 6 more

Open Access

https://doi.org/10.1038/s41598-017-15090-5

Copy DOI

Abstract

Accumulation of oxidized amino acids, including methionine, has been implicated in aging. The ability to reduce one of the products of methionine oxidation, free methionine-R-sulfoxide (Met-R-SO), is widespread in microorganisms, but during evolution this function, conferred by the enzyme fRMsr, was lost in metazoa. We examined whether restoration of the fRMsr function in an animal can alleviate the consequences of methionine oxidation. Ectopic expression of yeast fRMsr supported the ability of Drosophila to catalyze free Met-R-SO reduction without affecting fecundity, food consumption, and response to starvation. fRMsr expression also increased resistance to oxidative stress. Moreover, it extended lifespan of flies in a methionine-dependent manner. Thus, expression of an oxidoreductase lost during evolution can enhance metabolic and redox functions and lead to an increase in lifespan in an animal model. More broadly, our study exposes the potential of a combination of genetic and nutritional strategies in lifespan control.

Highlights

Molecular damage has been widely implicated in the aging process, including the damage caused by reactive oxygen species (ROS)[1,2,3,4]
The progeny of the cross among the three responder lines, the activator lines, and the control yw line were subjected to Western blotting (Fig. 1A and Supplementary Figure 1A) and free Met-R-SO reduction activity assays (Fig. 1B and Supplementary Figure 1B). fRMsr was highly expressed in da-GAL4 > fRMsr2.1 and da-GAL4 > fRMsr9.1 lines, expressed at a low level in da-GAL4 > fRMsr4.2 line, and was not detected in any of the control lines
Discussion fRMsr occurs across most prokaryotes and unicellular eukaryotes, where it catalyzes the reduction of free Met-R-SO

Summary

Introduction

Molecular damage has been widely implicated in the aging process, including the damage caused by reactive oxygen species (ROS)[1,2,3,4]. To prevent deleterious accumulation of oxidative damage, organisms use enzymes that participate in the removal of ROS or its consequences, often in cooperation with certain low molecular weight molecules One such strategy is to repair oxidized biomolecules, restoring their biological functions. Many oxidoreductases have been characterized for their contributions to redox homeostasis and aging such as thioredoxin reductase, methionine sulfoxide reductase (Msr), superoxide dismutase, catalase, and other enzymes[9] Several such enzymes rely on the reversible Cys and Met oxidation/reduction, including Msrs which reduces oxidized Met back to Met[10,11]. An additional Msr, fRMsr, was functionally characterized that possesses high efficiency in reducing free Met-R-SO, but this enzyme was lost in animals and many plants[13,14]. These flies efficiently reduced free Met-R-SO, and we further employed this model to examine the role of this process in lifespan control and other processes

Methods

Results

Conclusion