한빛사 논문
Abstract
Ara B. Hwanga, Eun-A Ryua, Murat Artana, Hsin-Wen Changb, Mohammad Humayun Kabirc, Hyun-Jun Nama, Dongyeop Leea, Jae-Seong Yanga,1, Sanguk Kima, William B. Maird, Cheolju Leec,e, Siu Sylvia Leeb, and Seung-Jae Leea,2
aDepartment of Life Sciences, Division of Information Technology Convergence Engineering, School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, South Korea;
bDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853;
cTheragnosis Research Center BRI, Korea Institute of Science and Technology, Seoul 136-791, South Korea;
dDepartment of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115; and
eDepartment of Biological Chemistry, University of Science and Technology, Daejeon 305-350, South Korea
Abstract
Mild inhibition of mitochondrial respiration extends the lifespan of many species. In Caenorhabditis elegans, reactive oxygen species (ROS) promote longevity by activating hypoxia-inducible factor 1 (HIF-1) in response to reduced mitochondrial respiration. However, the physiological role and mechanism of ROS-induced longevity are poorly understood. Here, we show that a modest increase in ROS increases the immunity and lifespan of C. elegans through feedback regulation by HIF-1 and AMP-activated protein kinase (AMPK). We found that activation of AMPK as well as HIF-1 mediates the longevity response to ROS. We further showed that AMPK reduces internal levels of ROS, whereas HIF-1 amplifies the levels of internal ROS under conditions that increase ROS. Moreover, mitochondrial ROS increase resistance to various pathogenic bacteria, suggesting a possible association between immunity and long lifespan. Thus, AMPK and HIF-1 may control immunity and longevity tightly by acting as feedback regulators of ROS.
aging, mitochondria, immunity, reactive oxygen species, C. elegans
1Present address: European Molecular Biology Laboratory, Center for Genomic Regulation Systems Biology Research Unit, Centre for Genomic Regulation, 08003 Barcelona, Spain.
2To whom correspondence should be addressed.
Author contributions: A.B.H., E.-A.R., S.K., C.L., S.S.L., and S.-J.L. designed research; A.B.H., E.-A.R., M.A., H.-W.C., M.H.K., D.L., and S.-J.L. performed research; W.B.M. contributed new reagents/analytic tools; A.B.H., E.-A.R., M.H.K., H.-J.N., J.-S.Y., C.L., and S.-J.L. analyzed data; and A.B.H., E.-A.R., and S.-J.L. wrote the paper.
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