Skip to main content
Dynamic Adaptation of Liver Mitochondria to Chronic Alcohol Feeding in Mice: BIOGENESIS, REMODELING, AND FUNCTIONAL ALTERATIONS
Journal of biochemistry (2012)
  • Derick Han, University of Southern California
  • Maria D. Ybanez, University of Southern California
  • Heather S. Johnson, University of Southern California
  • Janiece N. McDonald, University of Southern California
  • Lusine Mesropyan, University of Southern California
  • Harsh Sancheti
  • Gary G. Martin, Occidental College
  • Alanna Martin, Occidental College
  • Atalie M. Lim, University of Southern California
  • Lily Dara, University of Southern California
  • Enrique Cadenas, University of Southern California
  • Hidekazu Tsukamoto, University of Southern California
  • Niel Kaplowitz, University of Southern California
Liver mitochondria undergo dynamic alterations following chronic alcohol feeding to mice. Intragastric alcohol feeding to mice resulted in 1) increased state III respiration (109% compared with control) in isolated liver mitochondria, probably due to increased levels of complexes I, IV, and V being incorporated into the respiratory chain; 2) increased mitochondrial NAD+ and NADH levels (∼2-fold), with no change in the redox status; 3) alteration in mitochondrial morphology, with increased numbers of elongated mitochondria; and 4) enhanced mitochondrial biogenesis in the liver, which corresponded with an up-regulation of PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α). Oral alcohol feeding to mice, which is associated with less liver injury and steatosis, slightly enhanced respiration in isolated liver mitochondria (30.8% compared with control), lower than the striking increase caused by intragastric alcohol feeding. Mitochondrial respiration increased with both oral and intragastric alcohol feeding despite extensive N-acetylation of mitochondrial proteins. The alcohol-induced mitochondrial alterations are probably an adaptive response to enhance alcohol metabolism in the liver. Isolated liver mitochondria from alcohol-treated mice had a greater rate of acetaldehyde metabolism and respiration when treated with acetaldehyde than control. Aldehyde dehydrogenase-2 levels were unaltered in response to alcohol, suggesting that the greater acetaldehyde metabolism by isolated mitochondria from alcohol-treated mice was due to increased mitochondrial respiration that regenerated NAD+, the rate-limiting substrate in alcohol/acetaldehyde metabolism. Overall, our work suggests that mitochondrial plasticity in the liver may be an important adaptive response to the metabolic stress caused by alcohol intake and could potentially play a role in many other vital functions performed by the liver.
  • Alcohol,
  • Liver Injury,
  • Liver Metabolism,
  • Mitochondria,
  • Mitochondrial Metabolism
Publication Date
December 7, 2012
Citation Information
Derick Han, Maria D. Ybanez, Heather S. Johnson, Janiece N. McDonald, et al.. "Dynamic Adaptation of Liver Mitochondria to Chronic Alcohol Feeding in Mice: BIOGENESIS, REMODELING, AND FUNCTIONAL ALTERATIONS" Journal of biochemistry Vol. 287 (2012)
Available at: