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J Cell Sci. 2018 Aug 21;131(16). pii: jcs217331. doi: 10.1242/jcs.217331.

The putative ceramide-conjugation protein Cwh43 regulates G0 quiescence, nutrient metabolism and lipid homeostasis in fission yeast.

Author information

1
G0 Cell Unit, Okinawa Institute of Science and Technology Graduate University, Tancha 1919-1, Onna-son, Okinawa 904-0495, Japan nakazawa@oist.jp myanagid@gmail.com.
2
G0 Cell Unit, Okinawa Institute of Science and Technology Graduate University, Tancha 1919-1, Onna-son, Okinawa 904-0495, Japan.
3
Institute of Life Science, Kurume University, Hyakunen-Kohen 1-1, Kurume, Fukuoka 839-0864, Japan.

Abstract

Cellular nutrient states control whether cells proliferate, or whether they enter or exit quiescence. Here, we report characterizations of fission yeast temperature-sensitive (ts) mutants of the evolutionarily conserved transmembrane protein Cwh43, and explore its relevance to utilization of glucose, nitrogen source and lipids. GFP-tagged Cwh43 localizes at ER associated with the nuclear envelope and the plasma membrane, as in budding yeast. We found that cwh43 mutants failed to divide in low glucose and lost viability during quiescence under nitrogen starvation. In cwh43 mutants, comprehensive metabolome analysis demonstrated dramatic changes in marker metabolites that altered under low glucose and/or nitrogen starvation, although cwh43 cells apparently consumed glucose in the culture medium. Furthermore, we found that cwh43 mutant cells had elevated levels of triacylglycerols (TGs) and coenzyme A, and that they accumulated lipid droplets. Notably, TG biosynthesis was required to maintain cell division in the cwh43 mutant. Thus, Cwh43 affects utilization of glucose and nitrogen sources, as well as storage lipid metabolism. These results may fit a notion developed in budding yeast stating that Cwh43 conjugates ceramide to glycosylphosphatidylinositol (GPI)-anchored proteins and maintains integrity of membrane organization.

KEYWORDS:

Ceramide; Cwh43; Fission yeast; Lipid droplet; Low glucose; Nitrogen starvation

PMID:
30072439
DOI:
10.1242/jcs.217331
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Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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