Loss of tolerance to multiple environmental stresses due to limitation of structural diversity of complex sphingolipids.

Structural diversity of complex sphingolipids is important for maintenance of various cellular functions; however, the overall picture of the significance of this structural diversity remains largely unknown. To investigate the physiological importance of the structural diversity of complex sphingolipids, we here constructed a complex sphingolipid structural diversity disruption library in budding yeast, which comprises 11 mutants including with combinations of deletions of sphingolipid-metabolizing enzyme genes. The sensitivity of the mutants to various environmental stresses revealed that the more the structural variation of complex sphingolipids is limited, the more stress sensitivity tends to increase. Moreover, it was found that in mutant cells with only one subtype of complex sphingolipid, Slt2 MAP kinase and Msn2/4 transcriptional factors are essential for maintenance of a normal growth and compensation for reduced tolerance of multiple stresses caused by loss of complex sphingolipid diversity. Slt2 and Msn2/4 are involved in compensation for impaired integrity of cell walls and plasma membranes caused by loss of complex sphingolipid diversity, respectively. From these findings, it was suggested that loss of structural diversity of complex sphingolipids affects the environment of the cell surface, including both plasma membranes and cell walls, which could cause multiple environmental stress hypersensitivity.