ABSTRACT
Abstract .................................................................................................................. 414 Introduction ............................................................................................................ 414 Alcoholic Liver Disease ......................................................................................... 415
The Role of Mitochondria in Alcohol Metabolism in the Liver ....................... 415 Mitochondrial Dysfunction in ALD .................................................................. 415 Reassessment of Mitochondrial Alterations in ALD ......................................... 417 Mitochondrial Alterations Differ between Alcohol Animal Models ................. 417 Effect of Alcohol Feeding on Mitochondrial ROS Generation in the Liver ..... 419 JNK Translocation to Mitochondria May Mediate Apoptosis in ALD ............. 420
Nonalcoholic Fatty Liver Disease .......................................................................... 420 Pathology of NAFLD ........................................................................................ 420 Animal Models for NAFLD and NASH ........................................................... 421 Mitochondrial Alterations with NAFLD ........................................................... 421 Mitochondrial Bioenergetic Changes Associated with NAFLD ....................... 422 Mitochondria as Sources of ROS in NAFLFD ................................................. 423 Mitochondria as the Final Target of JNK-Induced Apoptosis in NAFLD ........ 423
Mitochondrial Dysfunction or Mitochondrial Adaptation in ALD and NAFLD ......423 Signaling Pathways Regulating Mitochondrial Dynamics and Adaptation ......424 Mitochondrial Dysfunction or Mitochondrial Adaptation in ALD ................... 425 Model of Mitochondrial Adaptation in ALD and NAFLD ............................... 427
References .............................................................................................................. 427
Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) have been traditionally linked with mitochondrial dysfunction in the liver. This may, however, be an incomplete description of mitochondrial dynamics that occur in the liver. Mitochondria can undergo many types of changes in response to stress or metabolic changes to help cells adapt. Metabolic stresses such as alcohol may cause some mitochondrial injury and damage. However, following injury, mitochondria can remodel and alter to help the liver adapt to stress. Dynamic mitochondrial remodeling and adaptation may be important mechanisms for the liver to deal with metabolic stresses that cause steatosis and, likely, the predominant, early mitochondrial alterations that occur in ALD and NAFLD.
