Human carbonyl reductase 4 is a mitochondrial NADPH-dependent quinone reductase

Biochem Biophys Res Commun. 2008 Dec 26;377(4):1326-30. doi: 10.1016/j.bbrc.2008.11.003. Epub 2008 Nov 10.


A protein encoded in the gene Cbr4 on human chromosome 4q32.3 belongs to the short-chain dehydrogenase/reductase family. Contrary to the functional annotation as carbonyl reductase 4 (CBR4), we show that the recombinant tetrameric protein, composed of 25-kDa subunits, exhibits NADPH-dependent reductase activity for o- and p-quinones, but not for other aldehydes and ketones. The enzyme was insensitive to dicumarol and quercetin, potent inhibitors of cytosolic quinone reductases. The 25-kDa CBR4 was detected in human liver, kidney and cell lines on Western blotting using anti-CBR4 antibodies. The overexpression of CBR4 in bovine endothelial cells reveals that the enzyme has a non-cleavable mitochondrial targeting signal. We further demonstrate that the in vitro quinone reduction by CBR4 generates superoxide through the redox cycling, and suggest that the enzyme may be involved in the induction of apoptosis by cytotoxic 9,10-phenanthrenequinone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apoptosis
  • Benzoquinones / chemistry
  • Benzoquinones / metabolism
  • Cell Line
  • Humans
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Molecular Sequence Data
  • NAD(P)H Dehydrogenase (Quinone) / chemistry
  • NAD(P)H Dehydrogenase (Quinone) / genetics
  • NAD(P)H Dehydrogenase (Quinone) / metabolism*
  • Oxidation-Reduction
  • Phenanthrenes / toxicity
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Superoxides / metabolism
  • Tissue Distribution


  • Benzoquinones
  • Mitochondrial Proteins
  • Phenanthrenes
  • Recombinant Proteins
  • Superoxides
  • quinone
  • 9,10-phenanthrenequinone
  • CBR4 protein, human
  • NAD(P)H Dehydrogenase (Quinone)