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 language | English |
|---|---|
| Pages (from-to) | 4872-4881 |
| Number of pages | 10 |
| Journal | Molecular and Cellular Biology |
| Volume | 26 |
| Issue number | 13 |
| DOIs | |
| State | Published - Jul 1 2006 |
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ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cell Biology
Cite this
Cytochrome c oxidase is required for the assembly/stability of respiratory complex I in mouse fibroblasts. / Diaz, Francisca; Fukui, Hirokazu; Garcia, Sofia; Moraes, Carlos T.
In: Molecular and Cellular Biology, Vol. 26, No. 13, 01.07.2006, p. 4872-4881.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cytochrome c oxidase is required for the assembly/stability of respiratory complex I in mouse fibroblasts
AU - Diaz, Francisca
AU - Fukui, Hirokazu
AU - Garcia, Sofia
AU - Moraes, Carlos T
PY - 2006/7/1
Y1 - 2006/7/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=33745478725&partnerID=8YFLogxK
U2 - 10.1128/MCB.01767-05
DO - 10.1128/MCB.01767-05
M3 - Article
C2 - 16782876
AN - SCOPUS:33745478725
VL - 26
SP - 4872
EP - 4881
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 13
ER -