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Mitochondrial Segregation in Budding Yeast Gametogenesis
- Sawyer, Eric M
- Advisor(s): Ünal, Elçin
Abstract
Cellular differentiation involves remodeling cellular architecture to transform one cell type into another. An important and conserved cellular differentiation program is gametogenesis, the process by which sexually reproducing organisms produce gametes. Gametogenesis involves specialized cell division as well as extensive cellular remodeling. Here, we investigated mitochondrial dynamics during gametogenesis in budding yeast to determine how regulators of meiotic differentiation act to control organelle morphogenesis. We found that mitochondria detach from the plasma membrane during meiosis II in a temporally controlled manner. Mitochondrial detachment is regulated by the induction of a transcription factor, Ndt80, which promotes the activation of a protein kinase, Ime2. Ime2 induces mitochondrial detachment by promoting the destruction of the mitochondria-endoplasmic reticulum-cortex anchor (MECA), which normally attaches mitochondria to the plasma membrane. Destruction of MECA involves Ime2-dependent phosphorylation and proteolysis that target both known subunits of the complex. We next investigated the fate of the mitochondrial network after its detachment. Consistent with previous studies, we found that the detached mitochondria gained associations with meiotic nuclei. By light and electron microscopy, we determined that the association between mitochondria and the nucleus is a developmentally regulated membrane contact site. Formation of the nucleus-mitochondria contact site required Ndt80 but not Ime2, indicating that the contact site is potentiated prior to destruction of MECA. We analyzed the potential involvement of two known ER-mitochondria tethers, ERMES and Ltc1/Lam6, but our data disfavor their potential roles in this process. Instead, novel factors are likely responsible for generating the nucleus-mitochondria contact site. Our study defines key mechanisms that coordinate mitochondrial morphogenesis with the landmark events of meiosis. Further, our work demonstrates that cells can developmentally regulate tethering to induce organelle remodeling.
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