Structural basis of mitochondrial membrane bending by the I-II-III2-IV2 supercomplex

Nature. 2023 Mar;615(7954):934-938. doi: 10.1038/s41586-023-05817-y. Epub 2023 Mar 22.


Mitochondrial energy conversion requires an intricate architecture of the inner mitochondrial membrane1. Here we show that a supercomplex containing all four respiratory chain components contributes to membrane curvature induction in ciliates. We report cryo-electron microscopy and cryo-tomography structures of the supercomplex that comprises 150 different proteins and 311 bound lipids, forming a stable 5.8-MDa assembly. Owing to subunit acquisition and extension, complex I associates with a complex IV dimer, generating a wedge-shaped gap that serves as a binding site for complex II. Together with a tilted complex III dimer association, it results in a curved membrane region. Using molecular dynamics simulations, we demonstrate that the divergent supercomplex actively contributes to the membrane curvature induction and tubulation of cristae. Our findings highlight how the evolution of protein subunits of respiratory complexes has led to the I-II-III2-IV2 supercomplex that contributes to the shaping of the bioenergetic membrane, thereby enabling its functional specialization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cryoelectron Microscopy*
  • Electron Transport
  • Electron Transport Complex I* / chemistry
  • Electron Transport Complex I* / metabolism
  • Electron Transport Complex I* / ultrastructure
  • Electron Transport Complex II* / chemistry
  • Electron Transport Complex II* / metabolism
  • Electron Transport Complex II* / ultrastructure
  • Electron Transport Complex III* / chemistry
  • Electron Transport Complex III* / metabolism
  • Electron Transport Complex III* / ultrastructure
  • Electron Transport Complex IV* / chemistry
  • Electron Transport Complex IV* / metabolism
  • Electron Transport Complex IV* / ultrastructure
  • Evolution, Molecular
  • Mitochondria* / chemistry
  • Mitochondria* / enzymology
  • Mitochondria* / metabolism
  • Mitochondria* / ultrastructure
  • Mitochondrial Membranes* / chemistry
  • Mitochondrial Membranes* / enzymology
  • Mitochondrial Membranes* / metabolism
  • Mitochondrial Membranes* / ultrastructure
  • Molecular Dynamics Simulation
  • Protein Multimerization
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism


  • Electron Transport Complex III
  • Electron Transport Complex IV
  • Electron Transport Complex II
  • Electron Transport Complex I
  • Protein Subunits