Intracellular transport and localization of microsomal cytochrome P450 |
| |
Authors: | Etienne P A Neve Magnus Ingelman-Sundberg |
| |
Institution: | 1.Section of Pharmacogenetics, Department of Physiology and Pharmacology,Karolinska Institutet,Stockholm,Sweden |
| |
Abstract: | The cytochrome P450 (P450) enzymes are mainly localized to the endoplasmic reticulum (ER), where they function within catalytic
complexes metabolizing xenobiotics and some endogenous substrates. However, certain members of families 1–3 were also found
in other subcellular compartments, such as mitochondria, plasma membrane, and lysosomes. The physiological function of these
enzymes in non-ER locations is not known, although plasma-membrane-associated P450s have been described to be catalytically
active and to participate in immune-mediated reactions with autoantibody formation that can trigger drug-induced hepatitis.
Several retention/retrieval mechanisms are active in the ER retention of the P450s and inverse integration of the translated
P450 into the ER membrane appears to be responsible for transport to the plasma membrane. Furthermore, hydrophilic motifs
in the NH2-terminal part have been suggested to be important for mitochondrial import. Phosphorylation of P450s has been described to
be important for increased rate of degradation as well as for targeting into mitochondria. It was also suggested that the
mitochondria-targeted P450s from families 1–3 could be active in drug metabolism using an alternative electron transport chain.
In this review we present an update of the field emphasizing studies concerning localization, posttranslational modification,
such as phosphorylation, and intracellular transport of microsomal P450s. |
| |
Keywords: | Microsomal P450s Mitochondria Phosphorylation Plasma membrane Protein targeting Degradation |
本文献已被 PubMed SpringerLink 等数据库收录! |
|