NADH-CYTOCHROME-B(5) REDUCTASE AND CYTOCHROME-B(5) ISOFORMS AS MODELSFOR THE STUDY OF POSTTRANSLATIONAL TARGETING TO THE ENDOPLASMIC-RETICULUM

Cytochrome b5 and NADH-cytochrome b5 reductase are integral membrane p roteins with cytosolic active domains and short membrane anchors, whic h are inserted post-translationally into their target membranes. Both are produced as different isoforms, with different localizations, in m ammalian cells. In the rat, the reductase gene generates two transcrip ts by an alternative promoter mechanism: a ubiquitous mRNA coding for the myristylated membrane-bound form, and an erythroid mRNA which gene rates both the soluble form and a nonmyristylated membrane-binding for m. The available evidence indicates that the ubiquitous myristylated f orm binds to the cytosolic face of both outer mitochondrial membranes and ER. In contrast, two genes code for two homologous forms of cytoch rome b5, one of which is found on outer mitochondrial membranes, the o ther on the ER. The gene specifying the ER form probably also generate s an erythroid-specific mRNA by alternative splicing, which codes for soluble cytochrome b5. Possible molecular mechanisms responsible for t he observed localizations of these different enzyme isoforms are discu ssed.