The architecture of respiratory supercomplexes

Nature. 2016 Sep 29;537(7622):644-648. doi: 10.1038/nature19774. Epub 2016 Sep 21.


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.

MeSH terms

  • Animals
  • Binding Sites
  • Catalytic Domain
  • Cell Respiration*
  • Cryoelectron Microscopy*
  • Electron Transport
  • Electron Transport Complex I / chemistry
  • Electron Transport Complex I / ultrastructure*
  • Electron Transport Complex III / chemistry
  • Electron Transport Complex III / ultrastructure*
  • Electron Transport Complex IV / chemistry
  • Electron Transport Complex IV / ultrastructure*
  • Heart
  • Mitochondria / enzymology
  • Mitochondria / metabolism
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Protein Stability
  • Protein Structure, Secondary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Reactive Oxygen Species / metabolism
  • Sheep


  • Protein Subunits
  • Reactive Oxygen Species
  • Electron Transport Complex IV
  • Electron Transport Complex I
  • Electron Transport Complex III