Inhibition of Respiration Extends C. elegans Life Span via Reactive Oxygen Species that Increase HIF-1 Activity
SCIE
SCOPUS
- Title
- Inhibition of Respiration Extends C. elegans Life Span via Reactive Oxygen Species that Increase HIF-1 Activity
- Authors
- Lee, SJ; Hwang, AB; Kenyon, C
- Date Issued
- 2010-12-07
- Publisher
- CELL PRESS
- Abstract
- A mild inhibition of mitochondrial respiration extends the life span of many organisms, including yeast, worms, flies, and mice [1-10], but the underlying mechanism is unknown. One environmental condition that reduces rates of respiration is hypoxia (low oxygen). Thus, it is possible that mechanisms that sense oxygen play a role in the longevity response to reduced respiration. The hypoxia-inducible factor HIF-1 is a highly conserved transcription factor that activates genes that promote survival during hypoxia [11, 12]. In this study, we show that inhibition of respiration in C. elegans can promote longevity by activating HIF-1. Through genome-wide screening, we found that RNA interference (RNAi) knockdown of many genes encoding respiratory-chain components induced hif-1-dependent transcription. Moreover, HIF-1 was required for the extended life spans of clk-1 and isp-1 mutants, which have reduced rates of respiration [1, 4, 13]. Inhibiting respiration appears to activate HIF-1 by elevating the level of reactive oxygen species (ROS). We found that ROS are increased in respiration mutants and that mild increases in ROS can stimulate HIF-1 to activate gene expression and promote longevity. In this way, HIF-1 appears to link respiratory stress in the mitochondria to a nuclear transcriptional response that promotes longevity.
- Keywords
- HYPOXIA-INDUCIBLE FACTOR; CAENORHABDITIS-ELEGANS; LONGEVITY; GENE; MICE; MITOCHONDRIA; DETERMINANT; BEHAVIOR; NEMATODE; MUTANTS
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/25189
- DOI
- 10.1016/J.CUB.2010.10.057
- ISSN
- 0960-9822
- Article Type
- Article
- Citation
- CURRENT BIOLOGY, vol. 20, no. 23, page. 2131 - 2136, 2010-12-07
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.