Structure of Mammalian Respiratory Supercomplex I1III2IV1

Cell. 2016 Dec 1;167(6):1598-1609.e10. doi: 10.1016/j.cell.2016.11.012.


The mammalian respiratory chain complexes assemble into supercomplexes (SCs) and reside in the inner mitochondrial membrane to transfer electrons and establish the proton gradient for complex V to synthesize ATP. The precise arrangement of SCs is largely unknown. Here, we report a 4.0-Å cryo-electron microscopy (cryo-EM) structure of the major SC in porcine heart, the 1.7-MDa SCI1III2IV1. The complex III (CIII) dimer and complex IV (CIV) bind at the same side of the L-shaped complex I (CI). Several accessory or supernumerary subunits of CI, such as NDUFA11, NDUFB4, NDUFB8, and NDUFB9, directly contribute to the oligomerization of CI, CIII, and CIV. COX7C and COX7A of CIV attach CIV to the concave surface formed by CIII and the distal end of membrane arm of CI. The structure suggests a possible mechanism by which electrons are transferred from NADH to cytochrome c and provides a platform for future functional dissection of respiration.

Keywords: electron transfer; membrane protein complex; mitochondria; oxidative phosphorylation; respiration; supercomplex.

MeSH terms

  • Animals
  • Cryoelectron Microscopy
  • Electron Transport*
  • Mitochondria, Heart / chemistry*
  • Mitochondrial Membranes / chemistry*
  • Models, Molecular
  • Multienzyme Complexes / chemistry
  • Proton Pumps / chemistry
  • Sus scrofa


  • Multienzyme Complexes
  • Proton Pumps