Functional characterization of human COQ4, a gene required for Coenzyme Q{sub 10} biosynthesis

Journal Article · Fri Jul 18 04:00:00 EDT 2008 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2008.04.172· OSTI ID:21143765

Casarin, Alberto ^[1]; Jimenez-Ortega, Jose Carlos ^[2]; Trevisson, Eva; Pertegato, Vanessa; Doimo, Mara; Ferrero-Gomez, Maria Lara; Abbadi, Sara ^[1]; Artuch, Rafael ^[3]; Quinzii, Catarina; Hirano, Michio ^[4]; Basso, Giuseppe ^[5]; Ocana, Carlos Santos; Navas, Placido ^[2]; Salviati, Leonardo ^[1]

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1. Clinical Genetics Unit, Department of Pediatrics, University of Padova, Via Giustiniani 3, 35128 Padova (Italy)
2. Centro Andaluz de Biologia del Desarrollo, Universidad Pablo de Olavide, Sevilla (Spain)
3. Biochemistry, Hospital Sant Joan de Deu, Barcelona (Spain)
4. Department of Neurology, Columbia University, New York, NY (United States)
5. Oncology/hematology laboratory, Department of Pediatrics, University of Padova (Italy)

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 {approx}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{sup null} yeast strains. Human COQ4 is an interesting candidate gene for patients with isolated CoQ{sub 10} deficiency.

• OSTI ID: 21143765
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 372; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINO ACIDS
BIOSYNTHESIS
CHROMOSOMES
GENES
GLYCEROL
HELA CELLS
LIVER
LUNGS
MITOCHONDRIA
NUCLEOTIDES
PANCREAS
PROTEINS
SACCHAROMYCES CEREVISIAE
TRANSCRIPTION
UBIQUINONE