| First Author | Kim SY | Year | 2018 |
| Journal | Autophagy | Volume | 14 |
| Issue | 1 | Pages | 152-168 |
| PubMed ID | 28841353 | Mgi Jnum | J:310433 |
| Mgi Id | MGI:6762544 | Doi | 10.1080/15548627.2017.1339001 |
| Citation | Kim SY, et al. (2018) ESRRA (estrogen-related receptor alpha) is a key coordinator of transcriptional and post-translational activation of autophagy to promote innate host defense. Autophagy 14(1):152-168 |
| abstractText | 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. |
