bioRxiv. 2024 Jan 17. pii: 2024.01.16.575914. [Epub ahead of print]
Young-Cheul Shin,
Pedro Latorre-Muro,
Amina Djurabekova,
Oleksii Zdorevskyi,
Christopher F Bennett,
Nils Burger,
Kangkang Song,
Chen Xu,
Vivek Sharma,
Maofu Liao,
Pere Puigserver.
In response to cold, mammals activate brown fat for respiratory-dependent thermogenesis reliant on the electron transport chain (1, 2). Yet, the structural basis of respiratory complex adaptation to cold remains elusive. Herein we combined thermoregulatory physiology and cryo-EM to study endogenous respiratory supercomplexes exposed to different temperatures. A cold-induced conformation of CI:III 2 (termed type 2) was identified with a ∼25° rotation of CIII 2 around its inter-dimer axis, shortening inter-complex Q exchange space, and exhibiting different catalytic states which favor electron transfer. Large-scale supercomplex simulations in lipid membrane reveal how unique lipid-protein arrangements stabilize type 2 complexes to enhance catalytic activity. Together, our cryo-EM studies, multiscale simulations and biochemical analyses unveil the mechanisms and dynamics of respiratory adaptation at the structural and energetic level.