Inhibition of elongin C promotes longevity and protein homeostasis via HIF‐1 in C. elegans

Aging Cell

Wooseon Hwang¹  Murat Artan³  Mihwa Seo⁴  Dongyeop Lee¹  Hong Gil Nam² 

[1] Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, South Korea;Center for Plant Aging Research, Institute for Basic Science, Daegu, South Korea;Information Technology Convergence Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, South Korea;School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, South Korea

关键词: aging;    C. elegans;    elc‐1;    hypoxia‐inducible factor 1;    protein homeostasis;   

DOI  :  10.1111/acel.12390

来源: Wiley

【 摘 要 】

Summary

The transcription factor hypoxia-inducible factor 1 (HIF-1) is crucial for responses to low oxygen and promotes longevity in Caenorhabditis elegans. We previously performed a genomewide RNA interference screen and identified many genes that act as potential negative regulators of HIF-1. Here, we functionally characterized these genes and found several novel genes that affected lifespan. The worm ortholog of elongin C, elc-1, encodes a subunit of E3 ligase and transcription elongation factor. We found that knockdown of elc-1 prolonged lifespan and delayed paralysis caused by impaired protein homeostasis. We further showed that elc-1 RNA interference increased lifespan and protein homeostasis by upregulating HIF-1. The roles of elongin C and HIF-1 are well conserved in eukaryotes. Thus, our study may provide insights into the aging regulatory pathway consisting of elongin C and HIF-1 in complex metazoans.

【 授权许可】

CC BY   
© 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.