Mechanisms of mitochondrial targeting of cytochrome P450 2E1: physiopathological role in liver injury and obesity.
Résumé
There has been growing evidence that phase I metabolizing enzymes cytochromes P450 (CYPs) are not only located in the endoplasmic reticulum but also in other subcellular compartments and particularly in mitochondria. The presence of CYPs in these organelles raises questions regarding their metabolic role and their possible deleterious effects on the respiratory chain complexes and mitochondrial DNA. This review will focus on one particular CYP, CYP2E1, which represents a significant source of reactive oxygen species and is involved in the metabolism of small molecule substrates including ethanol, drugs and carcinogens. Since hepatic CYP2E1 expression is increased in different physiopathological situations such as type 2 diabetes, obesity and ethanol intoxication, the presence of significant levels of this CYP within the mitochondria could have major deleterious effects. This review recalls the main data that brought to the fore the presence of CYP2E1 in mitochondria and the mechanism of its targeting in this organelle. The potential pathological consequences linked to the presence of CYP2E1 in mitochondria will be subsequently discussed.