Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov 14;187(23):6584-6598.e17.
doi: 10.1016/j.cell.2024.09.029. Epub 2024 Oct 11.

Structural basis of respiratory complex adaptation to cold temperatures

Young-Cheul Shin  1 , Pedro Latorre-Muro  2 , Amina Djurabekova  3 , Oleksii Zdorevskyi  3 , Christopher F Bennett  4 , Nils Burger  4 , Kangkang Song  5 , Chen Xu  5 , Joao A Paulo  6 , Steven P Gygi  6 , Vivek Sharma  7 , Maofu Liao  8 , Pere Puigserver  9
Affiliations

Structural basis of respiratory complex adaptation to cold temperatures

Young-Cheul Shin et al. Cell. .

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.

Keywords: CIII(2) rotation; brown adipose tissue; cellular adaptation; electron transport chain; membrane lipid remodeling; respiratory complexes.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Update of

References

    1. Cannon B, and Nedergaard J (2004). Brown adipose tissue: function and physiological significance. Physiol Rev 84, 277–359. 10.1152/physrev.00015.2003. - DOI - PubMed
    1. Peirce V, and Vidal-Puig A (2013). Regulation of glucose homoeostasis by brown adipose tissue. Lancet Diabetes Endocrinol 1, 353–360. 10.1016/S2213-8587(13)70055-X. - DOI - PubMed
    1. Kazak L, Chouchani ET, Jedrychowski MP, Erickson BK, Shinoda K, Cohen P, Vetrivelan R, Lu GZ, Laznik-Bogoslavski D, Hasenfuss SC, et al. (2015). A Creatine-Driven Substrate Cycle Enhances Energy Expenditure and Thermogenesis in Beige Fat. Cell 163, 643–655. 10.1016/j.cell.2015.09.035. - DOI - PMC - PubMed
    1. Latorre-Muro P, O’Malley KE, Bennett CF, Perry EA, Balsa E, Tavares CDJ, Jedrychowski M, Gygi SP, and Puigserver P (2021). A cold-stress-inducible PERK/OGT axis controls TOM70-assisted mitochondrial protein import and cristae formation. Cell Metab 33, 598–614.e7. 10.1016/j.cmet.2021.01.013. - DOI - PMC - PubMed
    1. Enerbäck S, Jacobsson A, Simpson EM, Guerra C, Yamashita H, Harper M-E, and Kozak LP (1997). Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 387, 90–94. 10.1038/258748a0. - DOI - PubMed

LinkOut - more resources