PER1 interaction with GPX1 regulates metabolic homeostasis under oxidative stress

Redox Biol. 2020 Oct:37:101694. doi: 10.1016/j.redox.2020.101694. Epub 2020 Aug 26.

Abstract

Metabolism serves mammalian feeding and active behavior, and is controlled by circadian clock. The molecular mechanism by which clock factors regulate metabolic homeostasis under oxidative stress is unclear. Here, we have characterized that the daily oxygen consumption rhythm was deregulated in Per1 deficient mice. Per1 deficiency impaired daily mitochondrial dynamics and deregulated cellular GPx-related ROS fluctuations in the peripheral organs. We identified that PER1 enhanced GPx activity through PER1/GPX1 interaction in cytoplasm, consequently improving the oxidative phosphorylation efficiency of mitochondria. Per1 expression was specifically elevated in the fasting peripheral organs for protecting mitochondrial from oxidation stress. These observations reveal that Per1-driven mitochondrial dynamics is a critical effector mechanism for the regulation of mitochondrial function in response to oxidation stress.

Keywords: GPX1; Metabolic rhythm; Oxidation stress; PER1; ROS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Circadian Clocks*
  • Circadian Rhythm
  • Glutathione Peroxidase / metabolism*
  • Glutathione Peroxidase GPX1
  • Homeostasis
  • Mice
  • Oxidative Stress*
  • Period Circadian Proteins* / genetics
  • Period Circadian Proteins* / metabolism
  • Transcription Factors

Substances

  • Per1 protein, mouse
  • Period Circadian Proteins
  • Transcription Factors
  • Glutathione Peroxidase
  • Glutathione Peroxidase GPX1
  • Gpx1 protein, mouse