Role of CYP2E1 in mitochondrial dysfunction and hepatic injury by alcohol and non-alcoholic substances

Mohamed A. Abdelmegeed, Seung Kwon Ha, Youngshim Choi, Mohammed Akbar, Byoung Joon Song

Research output: Contribution to journalReview article

Abstract

Alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD) are two pathological conditions that are spreading worldwide. Both conditions are remarkably similar with regard to the pathophysiological mechanism and progression despite different causes. Oxidative stressinduced mitochondrial dysfunction through post-translational protein modifications and/or mitochondrial DNA damage has been a major risk factor in both AFLD and NAFLD development and progression. Cytochrome P450-2E1 (CYP2E1), a known important inducer of oxidative radicals in the cells, has been reported to remarkably increase in both AFLD and NAFLD. Interestingly, CYP2E1 isoforms expressed in both endoplasmic reticulum (ER) and mitochondria, likely lead to the deleterious consequences in response to alcohol or in conditions of NAFLD after exposure to high fat diet (HFD) and in obesity and diabetes. Whether CYP2E1 in both ER and mitochondria work simultaneously or sequentially in various conditions and whether mitochondrial CYP2E1 may exert more pronounced effects on mitochondrial dysfunction in AFLD and NAFLD are unclear. The aims of this review are to briefly describe the role of CYP2E1 and resultant oxidative stress in promoting mitochondrial dysfunction and the development or progression of AFLD and NAFLD, to shed a light on the function of the mitochondrial CYP2E1 as compared with the ER-associated CYP2E1. We finally discuss translational research opportunities related to this field.

Original languageEnglish (US)
Pages (from-to)207-225
Number of pages19
JournalCurrent Molecular Pharmacology
Volume10
Issue number3
DOIs
StatePublished - Aug 1 2017
Externally publishedYes

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Cytochrome P-450 CYP2E1
Alcoholic Fatty Liver
Alcoholic Liver Diseases
Alcohols
Liver
Wounds and Injuries
Endoplasmic Reticulum
Mitochondria
Translational Medical Research
High Fat Diet
Post Translational Protein Processing
Mitochondrial DNA
DNA Damage
Disease Progression
Non-alcoholic Fatty Liver Disease
Protein Isoforms
Oxidative Stress
Obesity

Keywords

  • Alcoholic fatty liver disease
  • CYP2E1
  • Lipid peroxidation
  • Mitochondria
  • Mitochondrial dysfunction
  • Non-alcoholic fatty liver disease
  • Oxidative stress
  • Post-translational protein modification

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

Cite this

Role of CYP2E1 in mitochondrial dysfunction and hepatic injury by alcohol and non-alcoholic substances. / Abdelmegeed, Mohamed A.; Ha, Seung Kwon; Choi, Youngshim; Akbar, Mohammed; Song, Byoung Joon.

In: Current Molecular Pharmacology, Vol. 10, No. 3, 01.08.2017, p. 207-225.

Research output: Contribution to journalReview article

Abdelmegeed, Mohamed A. ; Ha, Seung Kwon ; Choi, Youngshim ; Akbar, Mohammed ; Song, Byoung Joon. / Role of CYP2E1 in mitochondrial dysfunction and hepatic injury by alcohol and non-alcoholic substances. In: Current Molecular Pharmacology. 2017 ; Vol. 10, No. 3. pp. 207-225.
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AB - Alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD) are two pathological conditions that are spreading worldwide. Both conditions are remarkably similar with regard to the pathophysiological mechanism and progression despite different causes. Oxidative stressinduced mitochondrial dysfunction through post-translational protein modifications and/or mitochondrial DNA damage has been a major risk factor in both AFLD and NAFLD development and progression. Cytochrome P450-2E1 (CYP2E1), a known important inducer of oxidative radicals in the cells, has been reported to remarkably increase in both AFLD and NAFLD. Interestingly, CYP2E1 isoforms expressed in both endoplasmic reticulum (ER) and mitochondria, likely lead to the deleterious consequences in response to alcohol or in conditions of NAFLD after exposure to high fat diet (HFD) and in obesity and diabetes. Whether CYP2E1 in both ER and mitochondria work simultaneously or sequentially in various conditions and whether mitochondrial CYP2E1 may exert more pronounced effects on mitochondrial dysfunction in AFLD and NAFLD are unclear. The aims of this review are to briefly describe the role of CYP2E1 and resultant oxidative stress in promoting mitochondrial dysfunction and the development or progression of AFLD and NAFLD, to shed a light on the function of the mitochondrial CYP2E1 as compared with the ER-associated CYP2E1. We finally discuss translational research opportunities related to this field.

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