Breaking the clip for cargo unloading from motor proteins: mechanism and significance

Abstract

The mitochondrion is an essential organelle involved in ATP generation, lipid metabolism, regulation of calci- um ions, etc. Therefore, it should be inherited properly by newly generated cells. In the budding yeast Saccha- romyces cerevisiae, mitochondria are passed on to daughter cells by the motor protein, Myo2, on the ac- tin cable. The mitochondria and Myo2 are connected via the adaptor protein Mmr1. After reaching daughter cells, mitochondria are released from the actin-myosin machinery and move dynamically. In our recent paper (Obara K et al. (2022), Nat Commun, doi:10.1038/s41467-022-29704-8), we demonstrated that the regulated proteolysis of Mmr1 is required for the unloading of mitochondria from Myo2 in daughter cells. Sequential post-translational modifications of Mmr1, i.e., phosphorylation followed by ubiquitination, are essential for Mmr1 degradation and mitochondrial release from Myo2. Defects in Mmr1 degradation cause stacking and deformation of mitochondria at the bud-tip and bud-neck, where Myo2 accumulates. Compared to wild-type cells, mutant cells with defects in Mmr1 degradation possess an elevated mitochon- drial membrane potential and produce higher levels of reactive oxygen species (ROS), along with hypersensi- tivity to oxidative stress.

Keywords

• mitochondria
• myosin
• mmr1
• ubiquitin
• proteasome
• proteolysis
• homeostasis
• saccharomyces cerevisiae