Mitochondrial complex I plays an essential role in human respirasome assembly

David Moreno-Lastres, Flavia Fontanesi, Inés García-Consuegra, Miguel A. Martín, Joaquín Arenas, Antoni Barrientos, Cristina Ugalde

Research output: Contribution to journalArticlepeer-review

178 Scopus citations


The biogenesis and function of the mitochondrial respiratory chain (RC) involve the organization of RC enzyme complexes in supercomplexes or respirasomes through an unknown biosynthetic process. This leads to structural interdependences between RC complexes, which are highly relevant from biological and biomedical perspectives, because RC defects often lead to severe neuromuscular disorders. We show that in human cells, respirasome biogenesis involves a complex I assembly intermediate acting as a scaffold for the combined incorporation of complexes III and IV subunits, rather than originating from the association of preassembled individual holoenzymes. The process ends with the incorporation of complex I NADH dehydrogenase catalytic module, which leads to the respirasome activation. While complexes III and IV assemble either as free holoenzymes or by incorporation of free subunits into supercomplexes, the respirasomes constitute the structural units where complex I is assembled and activated, thus explaining the significance of the respirasomes for RC function.

Original languageEnglish (US)
Pages (from-to)324-335
Number of pages12
JournalCell Metabolism
Issue number3
StatePublished - Mar 7 2012

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


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