Mechanisms of mitochondrial targeting of cytochrome P450 2E1: physiopathological role in liver injury and obesity.

Abstract

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.

• Authors: Laetitia Knockaert, Bernard Fromenty, Marie-Anne Robin
• Journal: The FEBS journal (FEBS J) Vol. 278 Issue 22 Pg. 4252-60 (Nov 2011) ISSN: 1742-4658 [Electronic] England
• PMID: 21929725 (Publication Type: Journal Article, Review)
• Copyright: Journal compilation © 2011 FEBS. No claim to original French government works.

Chemical References

• Anti-Infective Agents, Local
• Reactive Oxygen Species
• Ethanol
• Cytochrome P-450 CYP2E1

Topics

• Animals
• Anti-Infective Agents, Local (toxicity)
• Chemical and Drug Induced Liver Injury (physiopathology)
• Cytochrome P-450 CYP2E1 (metabolism)
• Ethanol (toxicity)
• Humans
• Mitochondria (metabolism)
• Obesity (physiopathology)
• Oxidative Stress
• Protein Transport
• Reactive Oxygen Species