A new shape, a new fate: uncovering how mitochondria regulate germline stem cell differentiation
Authors: Vernon Monteiro; Thomas Hurd
Affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
Keywords: h. mitochondria; b. germline stem cell
Stem cell differentiation is essential for development and tissue homeostasis. Often differentiation is accompanied by a rewiring of organelles and alterations of the metabolome. However, how mitochondrial dynamics contributes to, and influences differentiation in vivo remains poorly understood. Using the Drosophila germline as a model system, we find that remodelling of the inner mitochondrial membrane is coupled to germline stem cell (GSC) differentiation. During the early stages of differentiation, mitochondrial Complex V is essential to drive the remodelling of cristae and in its absence the immediate progeny fail to survive. The failure to remodel mitochondria during early germ cell differentiation results in activation the Integrated Stress Response through the ER membrane kinase, PERK. PERK does so by detecting alterations in the ER membrane. Furthermore, the loss of Complex V and the failure to remodel mitochondria, induces the formation of lipid droplets that is partially mediated through PERK activity. Taken together, our data suggest that the loss of inner mitochondrial remodelling during early germline stem cell differentiation destabilizes the ER membrane thereby activating PERK and inducing cell death.