4.8 Article

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

Journal

CELL
Volume 164, Issue 3, Pages 420-432

Publisher

CELL PRESS
DOI: 10.1016/j.cell.2015.12.020

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Funding

  1. HHMI
  2. Carnegie Institution for Science
  3. Jane Coffin Childs Research Fund

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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.

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