| First Author | Shi M | Year | 2021 |
| Journal | Nat Cell Biol | Volume | 23 |
| Issue | 3 | Pages | 268-277 |
| PubMed ID | 33664495 | Mgi Jnum | J:305261 |
| Mgi Id | MGI:6705764 | Doi | 10.1038/s41556-021-00642-9 |
| Citation | Shi M, et al. (2021) AIDA directly connects sympathetic innervation to adaptive thermogenesis by UCP1. Nat Cell Biol 23(3):268-277 |
| abstractText | The sympathetic nervous system-catecholamine-uncoupling protein 1 (UCP1) axis plays an essential role in non-shivering adaptive thermogenesis. However, whether there exists a direct effector that physically connects catecholamine signalling to UCP1 in response to acute cold is unknown. Here we report that outer mitochondrial membrane-located AIDA is phosphorylated at S161 by the catecholamine-activated protein kinase A (PKA). Phosphorylated AIDA translocates to the intermembrane space, where it binds to and activates the uncoupling activity of UCP1 by promoting cysteine oxidation of UCP1. Adipocyte-specific depletion of AIDA abrogates UCP1-dependent thermogenesis, resulting in hypothermia during acute cold exposure. Re-expression of S161A-AIDA, unlike wild-type AIDA, fails to restore the acute cold response in Aida-knockout mice. The PKA-AIDA-UCP1 axis is highly conserved in mammals, including hibernators. Denervation of the sympathetic postganglionic fibres abolishes cold-induced AIDA-dependent thermogenesis. These findings uncover a direct mechanistic link between sympathetic input and UCP1-mediated adaptive thermogenesis. |
