Respiratory complex III is required to maintain complex I in mammalian mitochondria

Rebeca Acín-Pérez, María Pilar Bayona-Bafaluy, Patricio Fernández-Silva, Raquel Moreno-Loshuertos, Acisclo Pérez-Martos, Claudio Bruno, Carlos T Moraes, José A. Enríquez

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274 Scopus citations


A puzzling observation in patients with oxidative phosphorylation (OXPHOS) deficiencies is the presence of combined enzyme complex defects associated with a genetic alteration in only one protein-coding gene. In particular, mutations in the mtDNA encoded cytochrome b gene are associated either with combined complex I+III deficiency or with only complex III deficiency. We have reproduced the combined complex I+III defect in mouse and human cultured cell models harboring cytochrome b mutations. In both, complex III assembly is impeded and causes a severe reduction in the amount of complex I, not observed when complex III activity was pharmacologically inhibited. Metabolic labeling in mouse cells revealed that complex I was assembled, although its stability was severely hampered. Conversely, complex III stability was not influenced by the absence of complex I. This structural dependence among complexes I and III was confirmed in a muscle biopsy of a patient harboring a nonsense cytochrome b mutation.

Original languageEnglish
Pages (from-to)805-815
Number of pages11
JournalMolecular Cell
Issue number6
StatePublished - Mar 26 2004


ASJC Scopus subject areas

  • Molecular Biology

Cite this

Acín-Pérez, R., Bayona-Bafaluy, M. P., Fernández-Silva, P., Moreno-Loshuertos, R., Pérez-Martos, A., Bruno, C., Moraes, C. T., & Enríquez, J. A. (2004). Respiratory complex III is required to maintain complex I in mammalian mitochondria. Molecular Cell, 13(6), 805-815.