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Molecular and Cellular Biology, July 2006, p. 4872-4881, Vol. 26, No. 13
0270-7306/06/$08.00+0     doi:10.1128/MCB.01767-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Cytochrome c Oxidase Is Required for the Assembly/Stability of Respiratory Complex I in Mouse Fibroblasts

Francisca Diaz,1 Hirokazu Fukui,2 Sofia Garcia,1 and Carlos T. Moraes1,2,3*

Department of Neurology,1 The Neuroscience Program,2 Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, Florida3

Received 8 September 2005/ Returned for modification 30 October 2005/ Accepted 18 April 2006

Cytochrome c oxidase (COX) biogenesis requires COX10, which encodes a protoheme:heme O farnesyl transferase that participates in the biosynthesis of heme a. We created COX10 knockout mouse cells that lacked cytochrome aa3, 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 IV is required for complex I assembly or stability.

* Corresponding author. Mailing address: University of Miami School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136. Phone: (305) 243-5858. Fax: (305) 243-3914. E-mail: cmoraes{at}med.miami.edu.

Molecular and Cellular Biology, July 2006, p. 4872-4881, Vol. 26, No. 13
0270-7306/06/$08.00+0     doi:10.1128/MCB.01767-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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