Prefoldin 6 mediates longevity response from heat shock factor 1 to FOXO in C. elegans

Heehwa G. Son, Keunhee Seo, Mihwa Seo, Sangsoon Park, Seokjin Ham, Seon Woo A. An, Eun Seok Choi, Yujin Lee, Haeshim Baek, Eunju Kim, Youngjae Ryu, Chang Man Ha, Ao Lin Hsu, Tae Young Roh, Sung Key Jang, Seung Jae V. Lee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Heat shock factor 1 (HSF-1) and forkhead box O (FOXO) are key transcription factors that protect cells from various stresses. In Caenorhabditis elegans, HSF-1 and FOXO together promote a long life span when insulin/IGF-1 signaling (IIS) is reduced. However, it remains poorly understood how HSF-1 and FOXO cooperate to confer IIS-mediated longevity. Here, we show that prefoldin 6 (PFD-6), a component of the molecular chaperone prefoldin-like complex, relays longevity response from HSF-1 to FOXO under reduced IIS. We found that PFD-6 was specifically required for reduced IIS-mediated longevity by acting in the intestine and hypodermis. We showed that HSF-1 increased the levels of PFD-6 proteins, which in turn directly bound FOXO and enhanced its transcriptional activity. Our work suggests that the prefoldin-like chaperone complex mediates longevity response from HSF-1 to FOXO to increase the life span in animals with reduced IIS.

Original languageEnglish
Pages (from-to)1562-1575
Number of pages14
JournalGenes and Development
Issue number23-24
StatePublished - 1 Dec 2018


  • Aging
  • C.elegans
  • DAF-16/FOXO
  • HSF-1/HSF1
  • PFD-6/PFDN6


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