Methionine sulfoxide reductase B in the endoplasmic reticulum is critical for stress resistance and aging in Drosophila

Do Hwan Lim, Jee Yun Han, Jae Ryong Kim, Young Sik Lee, Hwa Young Kim

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Methionine sulfoxide reductase B (MsrB) is an enzyme that repairs oxidatively damaged proteins by specifically reducing methionine-. R-sulfoxide back to methionine. Three MsrBs, localized in different cellular compartments, are expressed in mammals. However, the physiological roles of each MsrB with regard to its location remain poorly understood. Here, we expressed endoplasmic reticulum (ER)-targeted human MsrB3A (hMsrB3A) in Drosophila and examined its effects on various phenotypes. In two independent transgenic lines, both ubiquitous and neuronal expression of hMsrB3A rendered flies resistant to oxidative stress. Interestingly, these flies also showed significantly enhanced cold and heat tolerance. More strikingly, expression of hMsrB3A in the whole body and nervous system extended the lifespan of fruit flies at 29°C by 43-50% and 12-37%, respectively, suggesting that the targeted expression of MsrB in the ER regulates Drosophila lifespan. A significant increase in lifespan was also observed at 25°C only when hMsrB3A was expressed in neurons. Additionally, hMsrB3A overexpression significantly delayed the age-related decline in locomotor activity and fecundity. Taken together, our data provide evidence that the ER type of MsrB, MsrB3A, plays an important role in protection mechanisms against oxidative, cold and heat stresses and, moreover, in the regulation of fruit fly aging.

Original languageEnglish
Pages (from-to)20-26
Number of pages7
JournalBiochemical and biophysical research communications
Volume419
Issue number1
DOIs
Publication statusPublished - 2012 Mar 2

Bibliographical note

Funding Information:
We thank the Bloomington Stock Center and the Developmental Studies Hybridoma Bank for fly stocks and antibodies, respectively. This work was supported by the National Research Foundation of Korea (NRF) Grants 2009-0076059 (to Y.S.L.), 2010-0020596 and 2010-0001240 (to H.Y.K.) funded by the Ministry of Education, Science and Technology, and by Brain Korea 21 Project from the Ministry of Education, Science, and Technology of Korea (to Korea University). D.H.L. was supported by Hi Seoul Science/Humanities Fellowship from Seoul Scholarship Foundation.

Keywords

  • ER
  • Fruit fly
  • Lifespan
  • Methionine sulfoxide reductase
  • MsrB
  • Stress tolerance

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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