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Publication Abstract from PubMed

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.

Structural basis of respiratory complex adaptation to cold temperatures.,Shin YC, Latorre-Muro P, Djurabekova A, Zdorevskyi O, Bennett CF, Burger N, Song K, Xu C, Paulo JA, Gygi SP, Sharma V, Liao M, Puigserver P Cell. 2024 Oct 3:S0092-8674(24)01087-0. doi: 10.1016/j.cell.2024.09.029. PMID:39395414^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.