NADH-cytochrome b5 reductase and cytochrome b5 isoforms as models for the study of post-translational targeting to the endoplasmic reticulum

FEBS Lett. 1993 Jun 28;325(1-2):70-5. doi: 10.1016/0014-5793(93)81416-w.


Cytochrome b5 and NADH-cytochrome b5 reductase are integral membrane proteins with cytosolic active domains and short membrane anchors, which are inserted post-translationally into their target membranes. Both are produced as different isoforms, with different localizations, in mammalian cells. In the rat, the reductase gene generates two transcripts by an alternative promoter mechanism: a ubiquitous mRNA coding for the myristylated membrane-bound form, and an erythroid mRNA which generates both the soluble form and a nonmyristylated membrane-binding form. The available evidence indicates that the ubiquitous myristylated form binds to the cytosolic face of both outer mitochondrial membranes and ER. In contrast, two genes code for two homologous forms of cytochrome b5, one of which is found on outer mitochondrial membranes, the other on the ER. The gene specifying the ER form probably also generates an erythroid-specific mRNA by alternative splicing, which codes for soluble cytochrome b5. Possible molecular mechanisms responsible for the observed localizations of these different enzyme isoforms are discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cytochrome Reductases / genetics
  • Cytochrome Reductases / metabolism*
  • Cytochrome-B(5) Reductase
  • Cytochromes b5 / genetics
  • Cytochromes b5 / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • Intracellular Membranes / metabolism
  • Protein Processing, Post-Translational*
  • RNA, Messenger / metabolism


  • RNA, Messenger
  • Cytochromes b5
  • Cytochrome Reductases
  • Cytochrome-B(5) Reductase