ESRRA (estrogen-related receptor alpha) is a key coordinator of transcriptional and post-translational activation of autophagy to promote innate host defense
- Authors
- Kim, Soo Yeon; Yang, Chul-Su; Lee, Hye-Mi; Kim, Jin Kyung; Kim, Yi-Sak; Kim, Ye-Ram; Kim, Jae-Sung; Kim, Tae Sung; Yuk, Jae-Min; Dufour, Catherine Rosa; Lee, Sang-Hee; Kim, Jin-Man; Choi, Hueng-Sik; Giguere, Vincent; Jo, Eun-Kyeong
- Issue Date
- Dec-2017
- Publisher
- Landes Bioscience
- Keywords
- autophagy-related genes; estrogen-related receptor alpha; innate antimicrobial defense; Mycobacterium tuberculosis; post-translational modifications; sirtuin 1
- Citation
- Autophagy, v.14, no.1, pp 152 - 168
- Pages
- 17
- Indexed
- SCIE
SCOPUS
- Journal Title
- Autophagy
- Volume
- 14
- Number
- 1
- Start Page
- 152
- End Page
- 168
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/8040
- DOI
- 10.1080/15548627.2017.1339001
- ISSN
- 1554-8627
1554-8635
- Abstract
- The orphan nuclear receptor ESRRA (estrogen-related receptor alpha) is a key regulator of energy homeostasis and mitochondrial function. Macroautophagy/autophagy, an intracellular degradation process, is a critical innate effector against intracellular microbes. Here, we demonstrate that ESRRA is required for the activation of autophagy to promote innate antimicrobial defense against mycobacterial infection. AMP-activated protein kinase pathway and SIRT1 (sirtuin 1) activation led to induction of ESRRA, which is essential for autophagosome formation, in bone marrow-derived macrophages. ESRRA enhanced the transcriptional activation of numerous autophagy-related (Atg) genes containing ERR response elements in their promoter regions. Furthermore, ESRRA, operating in a feed-forward loop with SIRT1, was required for autophagy activation through deacetylation of ATG5, BECN1, and ATG7. Importantly, ESRRA deficiency resulted in a decrease of phagosomal maturation and antimicrobial responses against mycobacterial infection. Thus, we identify ESRRA as a critical activator of autophagy via both transcriptional and post-translational control to promote antimicrobial host responses.
- Files in This Item
-
Go to Link
- Appears in
Collections - COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY > ERICA 의약생명과학과 > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.