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ESRRA (estrogen-related receptor alpha) is a key coordinator of transcriptional and post-translational activation of autophagy to promote innate host defense

Title
ESRRA (estrogen-related receptor alpha) is a key coordinator of transcriptional and post-translational activation of autophagy to promote innate host defense
Author
양철수
Keywords
autophagy-related genes; estrogen-related receptor alpha; innate antimicrobial defense; Mycobacterium tuberculosis; post-translational modifications; sirtuin 1
Issue Date
2018-01
Publisher
TAYLOR & FRANCIS INC
Citation
AUTOPHAGY, v. 14, no. 1, page. 152-168
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.
URI
https://www.tandfonline.com/doi/full/10.1080/15548627.2017.1339001http://repository.hanyang.ac.kr/handle/20.500.11754/117247
ISSN
1554-8627; 1554-8635
DOI
10.1080/15548627.2017.1339001
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > BIONANOTECHNOLOGY(바이오나노학과) > Articles
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