Asymmetric inheritance of mitochondria in yeast

• Applicant: Professor Dr. Benedikt Westermann
• Subject Area: Cell Biology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 433461293

Mitochondria are essential organelles of eukaryotic cells. They have their own genome, which encodes a handful of mitochondrial proteins, and cannot be generated de novo. The inheritance of mitochondria during cell division requires the choreography of membrane fission and fusion processes with cytoskeleton-dependent transport of the organelles. In some cell types, mitochondria are partitioned asymmetrically, i.e. the daughter cells receive organelles with different properties. This serves, for example, to pass on healthy and fit mitochondria to the daughter cell that is determined to undergo a larger number of cell division cycles. Also yeast cells have the remarkable capacity to retain old and damaged mitochondria in the mother cell, while at the same time fit and metabolically active mitochondria are transported to the bud. The molecular mechanisms that determine the asymmetric distribution of mitochondria and the selection of healthy organelles for inheritance are largely unknown and are being studied using the yeast Saccharomyces cerevisiae as a model system. In our current work, we have developed an assay that allows us to observe the inheritance and dynamics of individual oxidatively damaged mitochondria in vivo. We were able to show that the adaptor protein Mmr1 acts as a molecular switch that regulates the binding of the myosin motor protein Myo2 to mitochondria. By releasing Myo2/Mmr1, damaged mitochondria are uncoupled from the actin-dependent transport machinery and thus immobilized in the mother cell. We have identified Alo1 as another mitochondrial outer membrane protein that is particularly important for mitochondrial inheritance during oxidative stress. We would now like to decipher the signals and mechanisms that recognize the oxidative damage in mitochondria and trigger the immobilization of dysfunctional organelles. We will then investigate the significance for cellular ageing. Furthermore, we will focus on the consequences of damage in the mitochondrial DNA as well as the role of cell cortex anchors and retrograde transport of mitochondria. This work is expected to provide a detailed understanding of the processes that determine the asymmetric inheritance of mitochondria and thus ageing of the cell.

• DFG Programme: Research Grants