Mammalian Mitochondrial Complex I Structure and Disease-Causing Mutations

Trends Cell Biol. 2018 Oct;28(10):835-867. doi: 10.1016/j.tcb.2018.06.006. Epub 2018 Jul 26.


Complex I has an essential role in ATP production by coupling electron transfer from NADH to quinone with translocation of protons across the inner mitochondrial membrane. Isolated complex I deficiency is a frequent cause of mitochondrial inherited diseases. Complex I has also been implicated in cancer, ageing, and neurodegenerative conditions. Until recently, the understanding of complex I deficiency on the molecular level was limited due to the lack of high-resolution structures of the enzyme. However, due to developments in single particle cryo-electron microscopy (cryo-EM), recent studies have reported nearly atomic resolution maps and models of mitochondrial complex I. These structures significantly add to our understanding of complex I mechanism and assembly. The disease-causing mutations are discussed here in their structural context.

Keywords: NADH–ubiquinone oxidoreductase; cryo-electron microscopy; mitochondrial disease; mitochondrial respiratory chain; respiratory complex I.

Publication types

  • Review

MeSH terms

  • Animals
  • Cryoelectron Microscopy
  • Electron Transport Complex I / chemistry*
  • Electron Transport Complex I / genetics*
  • Electron Transport Complex I / metabolism
  • Humans
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / metabolism
  • Mutation*
  • Protein Conformation


  • Electron Transport Complex I