During development, many cells such as oocytes, spores, seeds, muscle satellite cells, and certain types of immune cells, reduce their transcription and translation and enter a state of cellular quiescence. During this process, cells reduce their overall metabolic activity as means to protect the cell from oxidative damage and to maintain stored nutrients. However, the mechanisms that mediate these effects on metabolism during quiescence remain unclear. Using the Drosophila ovariole system we have found that a decrease in Insulin/Akt signaling triggers a remodeling of the mitochondria that promotes mitochondrial respiratory quiescence in mature oocytes. This effect is mediated by the conserved Akt target GSK3, which triggers a massive shift in the mitochondrial proteome. We are currently investigating the molecular mechanisms downstream of GSK3 that mediate remodeling of the mitochondrial proteome and induce mitochondrial respiratory quiescence.
Interestingly upon fertilization oocytes reactivate their mitochondria and increase their overall metabolic activity as a means to support the growth and development of the early embryo. Furthermore, We have found similar shifts in mitochondrial metabolism occur in developing mammalian tissues suggesting that dynamic changes in mitochondrial function may be a conserved aspect of quiescence and reactivation in many species. Despite these observations surprisingly little is known about the mechanism that underlies metabolic reactivation after quiescence. Our goal is to define these conserved mechanisms that mediate mitochondrial reactivation and to ascertain specific biosynthetic and energetic roles mitochondrial reactivation plays during development.