Electron Transport Chain Remodeling by GSK3 during Oogenesis Connects Nutrient State to Reproduction

Cell. 2016 Jan 28;164(3):420-32. doi: 10.1016/j.cell.2015.12.020.

Abstract

Reproduction is heavily influenced by nutrition and metabolic state. Many common reproductive disorders in humans are associated with diabetes and metabolic syndrome. We characterized the metabolic mechanisms that support oogenesis and found that mitochondria in mature Drosophila oocytes enter a low-activity state of respiratory quiescence by remodeling the electron transport chain (ETC). This shift in mitochondrial function leads to extensive glycogen accumulation late in oogenesis and is required for the developmental competence of the oocyte. Decreased insulin signaling initiates ETC remodeling and mitochondrial respiratory quiescence through glycogen synthase kinase 3 (GSK3). Intriguingly, we observed similar ETC remodeling and glycogen uptake in maturing Xenopus oocytes, suggesting that these processes are evolutionarily conserved aspects of oocyte development. Our studies reveal an important link between metabolism and oocyte maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / metabolism
  • Electron Transport Chain Complex Proteins / metabolism*
  • Embryo, Nonmammalian / metabolism
  • Embryonic Development
  • Female
  • Forkhead Transcription Factors / metabolism
  • Glycogen / metabolism*
  • Glycogen Synthase Kinase 3 / metabolism*
  • Mitochondria / metabolism
  • Oncogene Protein v-akt / metabolism
  • Oocytes / cytology
  • Oocytes / metabolism
  • Oogenesis*
  • Xenopus laevis / embryology*
  • Xenopus laevis / metabolism

Substances

  • Drosophila Proteins
  • Electron Transport Chain Complex Proteins
  • FOXO protein, Drosophila
  • Forkhead Transcription Factors
  • Glycogen
  • Oncogene Protein v-akt
  • Sgg protein, Drosophila
  • Glycogen Synthase Kinase 3