Open AccessIdentification of mouse sphingomyelin synthase 1 as a suppressor of Bax‐mediated cell death in yeast
Author(s) -
Yang Zhao,
Khoury Chamel,
JeanBaptiste Gaël,
Greenwood Michael T.
Publication year - 2006
Publication title -
fems yeast research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.991
H-Index - 92
eISSN - 1567-1364
pISSN - 1567-1356
DOI - 10.1111/j.1567-1364.2006.00052.x
Subject(s) - sphingomyelin , ceramide , sphingolipid , biology , ceramide synthase , biochemistry , atp synthase , sphingosine , microbiology and biotechnology , lipid signaling , yeast , enzyme , apoptosis , cholesterol , receptor
Abstract We have identified mouse sphingomyelin synthase 1 as a novel suppressor of the growth inhibitory effect of heterologously expressed Bax. Yeast cells expressing sphingomyelin synthase 1 were also found to show an increased resistance to a variety of cytotoxic stimuli including hydrogen peroxide, osmotic stress and elevated temperature. Sphingomyelin synthase 1 functions by catalyzing the conversion of ceramide and phosphatidylcholine to sphingomyelin and diacylglycerol. Ceramide is an antiproliferative and proapoptotic sphingolipid whose level increases in response to a variety of stresses. Consistent with its biochemical function, yeast cells expressing sphingomyelin synthase 1 have an enhanced ability to grow in media containing the cell‐permeable C 2 ‐ceramide analog as well as the ceramide precursor phytosphingosine. We also show that overexpression of AUR1 , a potential yeast functional homolog of sphingomyelin synthase, also protects cells from osmotic stress. Taken together, these results suggest that sphingomyelin synthase 1 likely prevents cell death by counteracting stress‐mediated accumulation of endogenous sphingolipids.