Author:
Shin Young-Cheul,Latorre-Muro Pedro,Djurabekova Amina,Zdorevskyi Oleksii,Bennett Christopher F.,Burger Nils,Song Kangkang,Xu Chen,Sharma Vivek,Liao Maofu,Puigserver Pere
Abstract
AbstractIn 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:III2(termed type 2) was identified with a ∼25° rotation of CIII2around 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.
Publisher
Cold Spring Harbor Laboratory