title: Mouse CLK-1 is imported into mitochondria by an unusual process that requires a leader sequence but no membrane potential.
abstract: clk-1 has been identified and characterized in the nematode Caenorhabditis elegans as a gene that affects the rates, regularity, and synchrony of physiological processes. The CLK-1 protein is mitochondrial and is required for ubiquinone biosynthesis in yeast and in worms, but its biochemical function remains unclear. We have studied the expression of murine mclk1 in a variety of tissues, and we find that the pattern of mclk1 mRNA accumulation closely resembles that of mitochondrial genes involved in oxidative phosphorylation. The pattern of protein accumulation, however, is sharply distinct in some tissues; mCLK1 appears relatively enriched in the gut and depleted in the nervous tissue. We also show that mCLK1 is synthesized as a preprotein that is imported into the mitochondrial matrix, where a leader sequence is cleaved off and the protein becomes loosely associated with the inner membrane. However, in contrast to all known mitochondrial proteins that contain a cleavable pre-sequence, the import of mCLK1 does not require a mitochondrial membrane potential.
authors.affiliation: Department of Biology, McGill University, H3A 1B1, Montréal, Québec, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Jiang
authors.forename: F
authors.initials: F
authors.lastname: Levavasseur
authors.forename: B
authors.initials: B
authors.lastname: McCright
authors.forename: E A
authors.initials: EA
authors.lastname: Shoubridge
authors.forename: S
authors.initials: S
authors.lastname: Hekimi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D002522:Chlorocebus aethiops; D003062:Codon / Q000235:genetics; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D024101:Mitochondrial Proteins; D006899:Mixed Function Oxygenases; D008969:Molecular Sequence Data; D010085:Oxidative Phosphorylation; D016133:Polymerase Chain Reaction; D021382:Protein Sorting Signals / Q000235:genetics; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: C104339:CLK-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D003062:Codon; D015801:Helminth Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D011994:Recombinant Proteins; D006899:Mixed Function Oxygenases; C434481:Coq7 protein, mouse