Young-Cheul Shin / Pedro Latorre-Muro / Amina Djurabekova / Oleksii Zdorevskyi / Christopher F Bennett / Nils Burger / Kangkang Song / Chen Xu / Joao A Paulo / Steven P Gygi / Vivek Sharma / Maofu Liao / Pere Puigserver /
PubMed 要旨
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 ...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 (termed type 2) supercomplex was identified with a ∼25° rotation of CIII 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.
EMDB-35314, PDB-8iap: Respiratory complex Peripheral Arm of CI, focus-refined map of type I, Wild type mouse under thermoneutral temperature 手法: EM (単粒子) / 解像度: 3.2 Å
EMDB-35315, PDB-8iaq: Respiratory complex Membrane domain of CI, focused map of type I, Wild type mouse under thermoneutral temperature 手法: EM (単粒子) / 解像度: 3.4 Å
EMDB-35332, PDB-8ib5: Respiratory complex Peripheral Arm of CI, focus-refined map of type IA, Wild type mouse under cold temperature 手法: EM (単粒子) / 解像度: 3.3 Å
EMDB-35333, PDB-8ib6: Respiratory complex Membrane domain of CI, focus-refined of type IA, Wild type mouse under cold temperature 手法: EM (単粒子) / 解像度: 3.3 Å
EMDB-35337, PDB-8iba: Respiratory complex Peripheral Arm of CI, focus-refined map of type IB, Wild type mouse under cold temperature 手法: EM (単粒子) / 解像度: 3.2 Å
EMDB-35338, PDB-8ibb: Respiratory complex Membrane domain of CI, focus-refined of type IB, Wild type mouse under cold temperature 手法: EM (単粒子) / 解像度: 3.3 Å
EMDB-35341, PDB-8ibe: Respiratory complex Peripheral Arm of CI, focus-refined map of type II, Wild type mouse under cold temperature 手法: EM (単粒子) / 解像度: 3.3 Å
EMDB-35342, PDB-8ibf: Respiratory complex Membrane domain of CI, focus-refined of type II, Wild type mouse under cold temperature 手法: EM (単粒子) / 解像度: 3.3 Å
EMDB-35353, PDB-8ic3: Respiratory complex Peripheral Arm of CI, focus-refined map of type I, PERK -/- mouse under cold temperature 手法: EM (単粒子) / 解像度: 3.2 Å
EMDB-35354, PDB-8ic4: Respiratory complex Membrane domain of CI, focus-refined of type I, PERK -/- mouse under cold temperature 手法: EM (単粒子) / 解像度: 3.2 Å
EMDB-38506, PDB-8xnl: Respiratory complex Peripheral Arm of CI, close form A, focus-refined map of type I, Wild type mouse under thermoneutral temperature 手法: EM (単粒子) / 解像度: 3.1 Å
EMDB-38507, PDB-8xnm: Respiratory complex Peripheral Arm of CI, close form B, focus-refined map of type I, Wild type mouse under thermoneutral temperature 手法: EM (単粒子) / 解像度: 3.5 Å
EMDB-38508, PDB-8xnn: Respiratory complex Peripheral Arm of CI, open form A, focus-refined map of type I, Wild type mouse under thermoneutral temperature 手法: EM (単粒子) / 解像度: 3.6 Å
EMDB-38509, PDB-8xno: Respiratory complex Peripheral Arm of CI, close form A, focus-refined map of type IA, Wild type mouse under Cold Acclimation 手法: EM (単粒子) / 解像度: 3.4 Å
EMDB-38510, PDB-8xnp: Respiratory complex Peripheral Arm of CI, close form B, focus-refined map of type IA, Wild type mouse under Cold Acclimation 手法: EM (単粒子) / 解像度: 3.5 Å
EMDB-38511, PDB-8xnq: Respiratory complex Peripheral Arm of CI, open form A, focus-refined map of type IA, Wild type mouse under Cold Acclimation 手法: EM (単粒子) / 解像度: 3.7 Å
EMDB-38512, PDB-8xnr: Respiratory complex Peripheral Arm of CI, close form A, focus-refined map of type IB, Wild type mouse under Cold Acclimation 手法: EM (単粒子) / 解像度: 3.3 Å
EMDB-38513, PDB-8xns: Respiratory complex Peripheral Arm of CI, close form B, focus-refined map of type IB, Wild type mouse under Cold Acclimation 手法: EM (単粒子) / 解像度: 3.5 Å
EMDB-38514, PDB-8xnt: Respiratory complex Peripheral Arm of CI, close form C, focus-refined map of type IB, Wild type mouse under Cold Acclimation 手法: EM (単粒子) / 解像度: 4.1 Å
EMDB-38515, PDB-8xnu: Respiratory complex Peripheral Arm of CI, open form A, focus-refined map of type IB, Wild type mouse under Cold Acclimation 手法: EM (単粒子) / 解像度: 3.6 Å
EMDB-38516, PDB-8xnv: Respiratory complex Peripheral Arm of CI, close form A, focus-refined map of type II, Wild type mouse under Cold Acclimation 手法: EM (単粒子) / 解像度: 3.3 Å
EMDB-38517, PDB-8xnw: Respiratory complex Peripheral Arm of CI, close form B, focus-refined map of type II, Wild type mouse under Cold Acclimation 手法: EM (単粒子) / 解像度: 3.6 Å
EMDB-38518, PDB-8xnx: Respiratory complex Peripheral Arm of CI, open form A, focus-refined map of type II, Wild type mouse under Cold Acclimation 手法: EM (単粒子) / 解像度: 3.5 Å
EMDB-38519, PDB-8xny: Respiratory complex Peripheral Arm of CI, open form B, focus-refined map of type II, Wild type mouse under Cold Acclimation 手法: EM (単粒子) / 解像度: 4.1 Å
EMDB-38520, PDB-8xnz: Respiratory complex Peripheral Arm of CI, close form A, focus-refined map of type I, PERK -/- mouse under Cold Acclimation 手法: EM (単粒子) / 解像度: 3.3 Å
EMDB-38521, PDB-8xo0: Respiratory complex Peripheral Arm of CI, close form B, focus-refined map of type I, PERK -/- mouse under Cold Acclimation 手法: EM (単粒子) / 解像度: 4.2 Å