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Respiratory complex Peripheral Arm of CI, open form A, focus-refined map of type I, Wild type mouse under thermoneutral temperature
Structural highlights
FunctionNDUAD_MOUSE Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Involved in the interferon/all-trans-retinoic acid (IFN/RA) induced cell death. This apoptotic activity is inhibited by interaction with viral IRF1. Prevents the transactivation of STAT3 target genes. May play a role in CARD15-mediated innate mucosal responses and serve to regulate intestinal epithelial cell responses to microbes.[UniProtKB:Q9P0J0] Publication Abstract from PubMedIn 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. References
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