A mitohormetic response to pro-oxidant exposure in the house mouse

Am J Physiol Regul Integr Comp Physiol. 2018 Jan 1;314(1):R122-R134. doi: 10.1152/ajpregu.00176.2017. Epub 2017 Sep 20.

Abstract

Mitochondria are hypothesized to display a biphasic response to reactive oxygen species (ROS) exposure. In this study, we evaluated the time course changes in mitochondrial performance and oxidative stress in house mice following X-irradiation. Forty-eight mice were equally divided among six groups, including a nonirradiated control and five experimental groups that varied in time between X-ray exposure and euthanasia (1 h and 1, 4, 7, and 10 days after X-irradiation). We measured parameters associated with mitochondrial respiratory function and ROS emission from isolated liver and skeletal muscle mitochondria and levels of oxidative damage and antioxidants in liver, skeletal muscle, and heart tissues. Mitochondrial function dropped initially after X-irradiation but recovered quickly and was elevated 10 days after the exposure. Hydrogen peroxide production, lipid peroxidation, and protein carbonylation showed inverse U-shaped curves, with levels returning to control or lower than control, 10 days after X-irradiation. Enzymatic antioxidants and markers for mitochondrial biogenesis exhibited a tissue-specific response after irradiation. These data provide the first chronological description of the mitohormetic response after a mild dose of irradiation and highlight the protective response that cells display to ROS exposure. This study also provides valuable information and application for future mitochondrial and oxidative stress studies in numerous physiological settings.

Keywords: mitochondrial function; mitohormesis; oxidative stress.

Publication types

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

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Electron Transport Chain Complex Proteins / metabolism
  • Female
  • Lipid Peroxidation / radiation effects
  • Mice
  • Mitochondria, Liver / metabolism
  • Mitochondria, Liver / pathology
  • Mitochondria, Liver / radiation effects*
  • Mitochondria, Muscle / metabolism
  • Mitochondria, Muscle / pathology
  • Mitochondria, Muscle / radiation effects*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / radiation effects*
  • Oxidative Stress / radiation effects*
  • Protein Carbonylation / radiation effects
  • Radiation Tolerance
  • Reactive Oxygen Species / metabolism
  • Time Factors

Substances

  • Antioxidants
  • Electron Transport Chain Complex Proteins
  • Reactive Oxygen Species