RRC ID 45753
Author Hwang AB, Ryu EA, Artan M, Chang HW, Kabir MH, Nam HJ, Lee D, Yang JS, Kim S, Mair WB, Lee C, Lee SS, Lee SJ.
Title Feedback regulation via AMPK and HIF-1 mediates ROS-dependent longevity in Caenorhabditis elegans.
Journal Proc Natl Acad Sci U S A
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.
Volume 111(42)
Pages E4458-67
Published 2014-10-21
DOI 10.1073/pnas.1411199111
PII 1411199111
PMID 25288734
PMC PMC4210294
MeSH AMP-Activated Protein Kinases / metabolism* Aging Animals Caenorhabditis elegans / immunology Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism* Cell Respiration Feedback, Physiological* Homeostasis Iron / chemistry Longevity / physiology Mitochondria / metabolism Mutation Paraquat / chemistry Phosphorylation Reactive Oxygen Species / metabolism* Transcription Factors / metabolism*
IF 9.412
Times Cited 80
C.elegans tm2986