Proteasomal regulation of the hypoxic response modulates aging in C. elegans

Ranjana Mehta, Katherine A. Steinkraus, George L. Sutphin, Fresnida J. Ramos, Lara S. Shamieh, Alexander Huh, Christina Davis, Devon Chandler-Brown, Matt Kaeberlein

Research output: Contribution to journalArticlepeer-review

178 Scopus citations

Abstract

The Caenorhabditis elegans von Hippel-Lindau tumor suppressor homolog VHL-1 is a cullin E3 ubiquitin ligase that negatively regulates the hypoxic response by promoting ubiquitination and degradation of the hypoxic response transcription factor HIF-1. Here, we report that loss of VHL-1 significantly increased life span and enhanced resistance to polyglutamine and β-amyloid toxicity. Deletion of HIF-1 was epistatic to VHL-1, indicating that HIF-1 acts downstream of VHL-1 to modulate aging and proteotoxicity. VHL-1 and HIF-1 control longevity by a mechanism distinct from both dietary restriction and insulin-like signaling. These findings define VHL-1 and the hypoxic response as an alternative longevity and protein homeostasis pathway.

Original languageEnglish (US)
Pages (from-to)1196-1198
Number of pages3
JournalScience
Volume324
Issue number5931
DOIs
StatePublished - May 29 2009
Externally publishedYes

ASJC Scopus subject areas

  • General

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