Cytochrome c oxidase is required for the assembly/stability of respiratory complex I in mouse fibroblasts

Francisca Diaz, Hirokazu Fukui, Sofia Garcia, Carlos T. Moraes

Research output: Contribution to journalArticle

157 Scopus citations

Abstract

Cytochrome c oxidase (COX) biogenesis requires COX10, which encodes a protoheme:heme O famesyl transferase that participates in the biosynthesis of heme a. We created COX10 knockout mouse cells that lacked cytochrome aa 3, were respiratory deficient, had no detectable complex IV activity, and were unable to assemble COX. Unexpectedly, the levels of respiratory complex I were markedly reduced in COX10 knockout clones. Pharmacological inhibition of COX did not affect the levels of complex I, and transduction of knockout cells with lentivirus expressing wild-type or mutant COX10 (retaining residual activity) restored complex I to normal levels. Pulse-chase experiments could not detect newly assembled complex I, suggesting that either COX is required for assembly of complex I or the latter is quickly degraded. These results suggest that in rapidly dividing cells, complex FV is required for complex I assembly or stability.

Original languageEnglish (US)
Pages (from-to)4872-4881
Number of pages10
JournalMolecular and cellular biology
Volume26
Issue number13
DOIs
StatePublished - Jul 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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