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Perturbation of sphingolipid metabolism induces endoplasmic reticulum stress‐mediated mitochondrial apoptosis in budding yeast
Author(s) -
Kajiwara Kentaro,
Muneoka Tetsuya,
Watanabe Yu,
Karashima Takefumi,
Kitagaki Hiroshi,
Funato Kouichi
Publication year - 2012
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12056
Subject(s) - endoplasmic reticulum , sphingolipid , biology , microbiology and biotechnology , programmed cell death , mitochondrion , unfolded protein response , apoptosis , cytosol , biochemistry , enzyme
Summary Sphingolipids are a class of membrane lipids conserved from yeast to mammals which determine whether a cell dies or survives. Perturbations in sphingolipid metabolism cause apoptotic cell death. Recent studies indicate that reduced sphingolipid levels trigger the cell death, but little is known about the mechanisms. In the budding yeast S accharomyces cerevisiae , we show that reduction in complex sphingolipid levels causes loss of viability, most likely due to the induction of mitochondria‐dependent apoptotic cell death pathway, accompanied by changes in mitochondrial and endoplasmic reticulum morphology and endoplasmic reticulum stress. Elevated cytosolic free calcium is required for the loss of viability. These results indicate that complex sphingolipids are essential for maintaining endoplasmic reticulum homeostasis and suggest that perturbation in complex sphingolipid levels activates an endoplasmic reticulum stress‐mediated and calcium‐dependent pathway to propagate apoptotic signals to the mitochondria.