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Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/40641
Title: Functional characterization of human COQ4, a gene required for Coenzyme Q10 biosynthesis
Authors: Casarin, Alberto; Jímenez-Ortega, José Carlos; Trevisson, Eva; Pertegato, Vanessa; Doimo, Mara; Ferrero-Gómez, María Lara; Abbadi, Sara; Artuch, Rafael; Quinzii, Catarina; Hirano, Michio; Basso, Giuseppe; Santos-Ocaña, Carlos; Navas, Plácido; Salviati, Leonardo
Keywords: Coenzyme Q10
Coenzyme Q10 deficiency
Green Fluorescent Proteins
Mitochondrial proteins
COQ4 protein
Issue Date: 18-May-2008
Publisher: Elsevier
Citation: Biochemical and Biophysical Research Communications 372(1): 35-39 (2008)
Abstract: Defects in genes involved in coenzyme Q (CoQ) biosynthesis cause primary CoQ deficiency, a severe multisystem disorders presenting as progressive encephalomyopathy and nephropathy. The COQ4 gene encodes an essential factor for biosynthesis in Saccharomyces cerevisiae. We have identified and cloned its human ortholog, COQ4, which is located on chromosome 9q34.13, and is transcribed into a 795 base-pair open reading frame, encoding a 265 amino acid (aa) protein (Isoform 1) with a predicted N-terminal mitochondrial targeting sequence. It shares 39% identity and 55% similarity with the yeast protein. Coq4 protein has no known enzymatic function, but may be a core component of multisubunit complex required for CoQ biosynthesis. The human transcript is detected in Northern blots as a approximately 1.4 kb single band and is expressed ubiquitously, but at high levels in liver, lung, and pancreas. Transcription initiates at multiple sites, located 333-23 nucleotides upstream of the ATG. A second group of transcripts originating inside intron 1 of the gene encodes a 241 aa protein, which lacks the mitochondrial targeting sequence (isoform 2). Expression of GFP-fusion proteins in HeLa cells confirmed that only isoform 1 is targeted to mitochondria. The functional significance of the second isoform is unknown. Human COQ4 isoform 1, expressed from a multicopy plasmid, efficiently restores both growth in glycerol, and CoQ content in COQ4(null) yeast strains. Human COQ4 is an interesting candidate gene for patients with isolated CoQ(10) deficiency.
Description: 5 páginas, 3 figuras.
Publisher version (URL): http://dx.doi.org/10.1016/j.bbrc.2008.04.172
URI: http://hdl.handle.net/10261/40641
DOI: 10.1016/j.bbrc.2008.04.172
ISSN: 0006-291X
References: PMID: 18474229
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