Swe1 delays cell cycle progression during impaired mitochondrial inheritance to promote mitochondrial homeostasis

Mitochondrial homeostasis is crucial for maintaining cellular health. Proper mitochondrial inheritance to daughter cells must be tightly regulated alongside growth and cell division in proliferating cells. In budding yeast, mitochondrial inheritance is ensured through active transport into the growing bud. While defects in inheritance are known to impact cell physiology, the mechanisms linking mitochondrial inheritance to cell cycle control are not fully understood.

Using cells lacking the mitochondrial inheritance adaptor Mmr1, researchers investigated the coordination between these processes. By analyzing over 8,000 budding events in real-time, they discovered that the duration of budding is directly related to the timing of mitochondrial inheritance. To further explore the underlying mechanism, the scientists conducted a genetic interaction screen using the auxin-inducible degron library.

Strains with defects in cell cycle regulators, especially those involved in mitotic progression, showed a high prevalence of synthetic growth defects. Among these, Swe1, a bud morphogenesis checkpoint kinase, was identified as a key factor influencing budding duration in response to impaired mitochondrial inheritance.

Depleting both Mmr1 and Swe1 significantly reduced the impact of mitochondrial inheritance on the lengthening of budding duration, resulting in a substantial number of daughter cells with inadequate mitochondrial supply. The researchers propose a regulatory loop called MIBA (mitochondrial inheritance-dependent budding adaptation) to describe this process.

Overall, these findings uncover a mechanism by which cells link mitochondrial inheritance to cell cycle progression, emphasizing the significance of this coupling for maintaining mitochondrial homeostasis within the population.