Autophagy, 2017, 01, 1─17, DOI: https://doi.org/10.1080/15548627.2017.1339001

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

soo yoen kim, Chul-Su Yang ; Hye-Mi Lee; Jin Kyung Kim; Yi-Sak Kim; Ye-Ram Kim; Jae-Sung Kim; Tae Sung Kim; Jae-Min Yuk; Catherine Rosa Dufour; Sang-Hee Lee; Jin-Man Kim; Hueng-Sik Choi; Vincent Gigu？re; Eun-Kyeong Jo

Abstract

The orphan nuclear receptor ESRRA (estrogen-related receptor α) 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 tranional 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 tranional and post-translational control to promote antimicrobial host responses.

• DOI: https://doi.org/10.1080/15548627.2017.1339001
• ISBN or ISSN: 1554-8627

• 본 연구는 질병관리본부 연구개발과제(과제번호 2017-보건의료생물자원종합관리) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2017-보건의료생물자원종합관리) by Research of Korea Centers for Disease Control and Prevention.