During budding yeast cell division, mother cells increase their replicative age while daughter cells are rejuvenated. Although loss of the gene encoding yeast ceramide synthase Lag1 (Δlag1) increases replicative life span, deletion of its homolog Lac1 (Δlac1) does not. In this work, Maya Schuldiner, Anthony H. Futerman, Yves Barral and colleagues (Megyeri et al., 2019) uncover differences in Lag1 and Lac1 specificity that might explain these observations. Yeast synthesize two different classes of sphingolipids (SLs): dihydro-SLs and phyto-SLs. The authors show that in cells that can only produce dihydro-SLs (Δsur2), Δlac1, but not Δlag1, changes total sphingolipid levels, suggesting that Lag1 is less important for dihydrosphingolipid synthesis. Accordingly, Δlac1 Δsur2 strains show lower resistance to heat stress (which requires SL synthesis) and reduced de novo SL synthesis than Δlag1 Δsur2 strains. Using in vitro assays, the authors further demonstrate that Lag1 has a higher affinity for phytosphingosine than Lac1. Interestingly, phyto-SLs are essential to the formation of the diffusion barriers in the ER membrane and nuclear envelope that prevent the diffusion of senescence factors to the daughter cell during cell division. Indeed, the authors show that diffusion barrier function in the nuclear envelope is impaired in Δlag1 cells, but not in Δlac1 cells. Collectively, these results suggest that by preferentially promoting the synthesis of phyto-SLs, Lag1 allows the establishment of diffusion barriers that prevent the spread of senescence factors to daughter cells during cell division.

• © 2019. Published by The Company of Biologists Ltd