| First Author | Shin YC | Year | 2024 |
| Journal | Cell | Volume | 187 |
| Issue | 23 | Pages | 6584-6598.e17 |
| PubMed ID | 39395414 | Mgi Jnum | J:358175 |
| Mgi Id | MGI:7779274 | Doi | 10.1016/j.cell.2024.09.029 |
| Citation | Shin YC, et al. (2024) Structural basis of respiratory complex adaptation to cold temperatures. Cell |
| abstractText | In response to cold, mammals activate brown fat for respiratory-dependent thermogenesis reliant on the electron transport chain. Yet, the structural basis of respiratory complex adaptation upon cold exposure remains elusive. Herein, we combined thermoregulatory physiology and cryoelectron microscopy (cryo-EM) to study endogenous respiratory supercomplexes from mice exposed to different temperatures. A cold-induced conformation of CI:III(2) (termed type 2) supercomplex was identified with a approximately 25 degrees rotation of CIII(2) around its inter-dimer axis, shortening inter-complex Q exchange space, and exhibiting catalytic states that favor electron transfer. Large-scale supercomplex simulations in mitochondrial membranes reveal how lipid-protein arrangements stabilize type 2 complexes to enhance catalytic activity. Together, our cryo-EM studies, multiscale simulations, and biochemical analyses unveil the thermoregulatory mechanisms and dynamics of increased respiratory capacity in brown fat at the structural and energetic level. |
