title: A selective requirement for copper-dependent activation of cytochrome c oxidase by Cox17p.
abstract: Cox17p is cloned from yeast as a chaperone to deliver copper to the mitochondria of assembly for cytochrome c oxidase (CCO). In mammals, CCO is a key enzyme for cellular respiration and a defect in its function is associated with severe neonatal or infantile lactic acidosis and early death. Recently, we found that Cox17p is not only required for mitochondrial oxidative phosphorylation but also is essential for embryonic growth and development in COX17 gene-deficient mice. To investigate its biochemical features, recombinant human Cox17p was overexpressed and purified without a purification tag. It specifically binds Cu(I) at a molar copper content of 3.3+/-0.04 under reduced conditions and significantly activates the mitochondrial CCO in vitro. Although the Cu-Cox17p complex was maintained between pH values from 5.0 to 7.7, Cu was completely released from Cox17p at pH 8.0. An acute exposure of excess amount of copper ion to mouse cells resulted in a significant reduction of Cox17p mRNA expression, whereas copper starvation maintained the Cox17p transcription level. These results suggest that the stringent selectivity of Cox17p for copper is required for CCO activation, to prevent copper overload, or promote the supply of copper.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tenno-dai, Tsukuba, Ibaraki 305-8572, Japan. JAB03176@nifty.ne.jp
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kako
authors.forename: Akio
authors.initials: A
authors.lastname: Takehara
authors.forename: Hidenori
authors.initials: H
authors.lastname: Arai
authors.forename: Takashi
authors.initials: T
authors.lastname: Onodera
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hanagata
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Ogra
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takagi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kodama
authors.forename: Kazuo T
authors.initials: KT
authors.lastname: Suzuki
authors.forename: Eisuke
authors.initials: E
authors.lastname: Munekata
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology; D000079922:Copper Transport Proteins; D003576:Electron Transport Complex IV / Q000378:metabolism*; D004789:Enzyme Activation; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D019216:Metals, Heavy / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C491006:COX17 protein, human; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; D019216:Metals, Heavy; D012333:RNA, Messenger; D003300:Copper; D003576:Electron Transport Complex IV