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The architecture of respiratory supercomplexes

Author

Listed:
  • James A. Letts

    (Institute of Science and Technology Austria)

  • Karol Fiedorczuk

    (Institute of Science and Technology Austria
    MRC Mitochondrial Biology Unit)

  • Leonid A. Sazanov

    (Institute of Science and Technology Austria)

Abstract

Mitochondrial electron transport chain complexes are organized into supercomplexes responsible for carrying out cellular respiration. Here we present three architectures of mammalian (ovine) supercomplexes determined by cryo-electron microscopy. We identify two distinct arrangements of supercomplex CICIII2CIV (the respirasome)—a major ‘tight’ form and a minor ‘loose’ form (resolved at the resolution of 5.8 Å and 6.7 Å, respectively), which may represent different stages in supercomplex assembly or disassembly. We have also determined an architecture of supercomplex CICIII2 at 7.8 Å resolution. All observed density can be attributed to the known 80 subunits of the individual complexes, including 132 transmembrane helices. The individual complexes form tight interactions that vary between the architectures, with complex IV subunit COX7a switching contact from complex III to complex I. The arrangement of active sites within the supercomplex may help control reactive oxygen species production. To our knowledge, these are the first complete architectures of the dominant, physiologically relevant state of the electron transport chain.

Suggested Citation

  • James A. Letts & Karol Fiedorczuk & Leonid A. Sazanov, 2016. "The architecture of respiratory supercomplexes," Nature, Nature, vol. 537(7622), pages 644-648, September.
    • Handle: RePEc:nat:nature:v:537:y:2016:i:7622:d:10.1038_nature19774
    DOI: 10.1038/nature19774
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    Cited by:

    1. Enrique Balderas & David R. Eberhardt & Sandra Lee & John M. Pleinis & Salah Sommakia & Anthony M. Balynas & Xue Yin & Mitchell C. Parker & Colin T. Maguire & Scott Cho & Marta W. Szulik & Anna Bakhti, 2022. "Mitochondrial calcium uniporter stabilization preserves energetic homeostasis during Complex I impairment," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Daniel Riepl & Ana P. Gamiz-Hernandez & Terezia Kovalova & Sylwia M. Król & Sophie L. Mader & Dan Sjöstrand & Martin Högbom & Peter Brzezinski & Ville R. I. Kaila, 2024. "Long-range charge transfer mechanism of the III2IV2 mycobacterial supercomplex," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Ami Kobayashi & Kotaro Azuma & Toshihiko Takeiwa & Toshimori Kitami & Kuniko Horie & Kazuhiro Ikeda & Satoshi Inoue, 2023. "A FRET-based respirasome assembly screen identifies spleen tyrosine kinase as a target to improve muscle mitochondrial respiration and exercise performance in mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Fangzhu Han & Yiqi Hu & Mengchen Wu & Zhaoxiang He & Hongtao Tian & Long Zhou, 2023. "Structures of Tetrahymena thermophila respiratory megacomplexes on the tubular mitochondrial cristae," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    5. Zhaoxiang He & Mengchen Wu & Hongtao Tian & Liangdong Wang & Yiqi Hu & Fangzhu Han & Jiancang Zhou & Yong Wang & Long Zhou, 2024. "Euglena’s atypical respiratory chain adapts to the discoidal cristae and flexible metabolism," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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