Cytochrome c oxidase is required for the assembly/stability of respiratory complex I in mouse fibroblasts.
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.
Diaz
Francisca
F
Department of Neurology, University of Miami School of Medicine, 1095 NW 14 Terrace, Miami, FL 33136, USA.
Fukui
Hirokazu
H
Garcia
Sofia
S
Moraes
Carlos T
CT
D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002308:Cardiolipins / Q000032:analysis / Q000378:metabolism; D042967:Electron Transport Complex I / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000235:genetics / Q000502:physiology*; D004795:Enzyme Stability; D005347:Fibroblasts / Q000201:enzymology; D017353:Gene Deletion; D006418:Heme / Q000031:analogs & derivatives / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology / Q000648:ultrastructure; D017354:Point Mutation; D014162:Transfection
D002308:Cardiolipins; D008565:Membrane Proteins; C027728:heme a; D006418:Heme; D003576:Electron Transport Complex IV; D019883:Alkyl and Aryl Transferases; C512252:COX10 protein, mouse; D042967:Electron Transport Complex I