Life is dependent on the protection of cellular functions from various stresses. Sphingolipids are essential biomembrane components in eukaryotic organisms, which are exposed to risks that may disrupt sphingolipid metabolism, threatening their lives. Defects of the sphingolipid biosynthesis pathway cause profound defects of various cellular functions and ultimately cell death. Therefore, cells are equipped with defense response mechanisms against aberrant metabolism of sphingolipids, the most characterized one being the target of rapamycin complex 2-mediated regulation of sphingolipid biosynthesis in budding yeast Saccharomyces cerevisiae. On the other hand, very recently, we found that the high osmolarity glycerol pathway is involved in suppression of a growth defect caused by a reduction in complex sphingolipid levels in yeast. It is suggested that this signaling pathway is not involved in the repair of the impaired biosynthesis pathway for sphingolipids, but compensates for cellular dysfunctions caused by reduction in complex sphingolipid levels. This is a novel protection mechanism against aberrant metabolism of complex sphingolipids, and further investigation of the mechanism will provide new insights into the physiological significance of complex sphingolipids. Here, we summarize the response signaling against breakdown of sphingolipid biosynthesis in yeast, which includes the high osmolarity glycerol pathway.
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