EMD-35313
Respiratory complex CI:CIII2, type I, Wild type mouse under thermoneutral temperature
EMD-35313
Single-particle4.2 Å
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Map released: 18/09/2024
Last modified: 04/12/2024
Sample Organism:
Mus musculus
Sample: Respiratory Supercomplex CI:CIII2
Fitted models: 8iao (Avg. Q-score: 0.295)
Deposition Authors: Shin Y-C
,
Liao M
Sample: Respiratory Supercomplex CI:CIII2
Fitted models: 8iao (Avg. Q-score: 0.295)
Deposition Authors: Shin Y-C
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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
(2024) Cell , 187 , 6584
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(2024) Cell , 187 , 6584
Abstract:
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:III2 (termed type 2) supercomplex was identified with a ∼25° rotation of CIII2 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.
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:III2 (termed type 2) supercomplex was identified with a ∼25° rotation of CIII2 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.