The Drosophila homolog of methionine sulfoxide reductase A extends lifespan and increases nuclear localization of FOXO

Edited by Vladimir Skulachev

Received 30 March 2010; received in revised form 28 June 2010; accepted 19 July 2010. published online 23 July 2010.

Abstract

Methionine sulfoxide reductase A (msrA) was previously found to increase resistance to oxidative stress and longevity in animals. We identified Drosophila msrA (dmsrA), a Drosophila homolog of human msrA, as a downstream effector of forkhead box O (FOXO) signaling in Drosophila, which enhances resistance to oxidative stress and increases survival under stressed conditions. Additionally, overexpression of dmsrA in neurons extended the lifespan of flies. Moreover, overexpression of dmsrA in fat body cells caused FOXO to translocate to the nucleus, implying that this possible positive feedback loop between dmsrA and FOXO could potentiate the antioxidant activity of dmsrA and increase the lifespan in Drosophila.

Abbreviations: JNK, c-Jun N-terminal kinase, dFOXO, Drosophila FOXO, dmsrA, Drosophila msrA, FOXO, forkhead box O, msrA, methionine sulfoxide reductase A, Prx II, Peroxiredoxin II, UAS, upstream activator sequence, GMR, glass multiple reporter

Keywords: Antioxidant enzyme, Drosophila, Forkhead box O, Lifespan, Longevity, Methionine sulfoxide reductase A, Oxidative stress, Transcription, Translocation

a Department of Ophthalmology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea

b Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea

c Myunggok Eye Research Institute, Kim’s Eye Hospital, Konyang University College of Medicine, Seoul, Republic of Korea

d Department of Environmental Engineering, Chosun University, Gwangju, Republic of Korea

Corresponding author. Address: Aging Research Center, KRIBB, Daejeon, Republic of Korea. Fax: +82 42 860 4608.

Corresponding author. Address: Myunggok Eye Research Institute, Kim’s Eye Hospital, 156, 4ga, Yeoungdeungpo-dong, Yeoungdeungpo-gu, Seoul, Republic of Korea. Fax: +82 2 2633 3976.

1 These authors contributed equally to this work and should be considered co-first authors.

PII: S0014-5793(10)00591-0

doi:10.1016/j.febslet.2010.07.033

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