Interleukin-6 is an important mediator for mitochondrial DNA repair after alcoholic liver injury in mice

Hepatology. 2010 Dec;52(6):2137-47. doi: 10.1002/hep.23909. Epub 2010 Oct 7.

Abstract

We investigated the hypothesis that a prominent effect of chronic ethanol consumption is mitochondrial DNA (mtDNA) injury and compared this injury in IL-6 knockout (KO) and wild-type (WT) mice. Ethanol feeding for 4 weeks resulted in steatosis and oxidative mtDNA damage (8-OHdG) in both IL-6KO and WT mice. However, the WT mice were able to repair the injury by increased production of mtDNA repair enzymes (OGG-1, Neil 1) and check point (p21, p53) proteins and avoid the mtDNA mutations. By contrast the IL-6 KO mice were unable to repair mtDNA resulting in deletions and diminished transcription of the mtDNA encoded protein cytochrome c oxidase subunit-I (COI). The mitochondrial injury was reflected by decreased membrane potential, reduced levels of ATP, and apoptosis-inducing factor (AIF)-induced apoptosis.

Conclusion: IL-6 plays a critical role in allowing the liver to recover from significant mtDNA oxidation caused by alcohol. The data suggests that IL-6 activates mtDNA repair enzymes and induces cell cycle arrest allowing time for mtDNA repair.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 3 / metabolism
  • DNA Repair*
  • DNA, Mitochondrial / metabolism*
  • Interleukin-6 / physiology*
  • Liver / drug effects
  • Liver Diseases, Alcoholic / metabolism*
  • Liver Diseases, Alcoholic / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Mitochondria, Liver / drug effects*

Substances

  • DNA, Mitochondrial
  • Interleukin-6
  • Casp3 protein, mouse
  • Caspase 3