Schizosaccharomyces pombe Cells Deficient in Triacylglycerols Synthesis Undergo Apoptosis upon Entry into the Stationary Phase

Zhang, Qian; Chieu, Hai Kee; Low, Choon Pei; Zhang, Shaochong; Heng, Chew-Kiat; Yang, Hongyuan

doi:10.1074/jbc.m306998200

Cited by 119 publications

(137 citation statements)

References 53 publications

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“…1J Inset) also became deformed. Unexpectedly, the intranuclear vesicle-like structures may be lipid containing, as they were stained by Nile red that was used to reveal lipid droplets (storage particles) normally present in cytoplasm (19) (Fig. S3).…”

Section: Resultsmentioning

confidence: 99%

Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast

Takeda

Yoshida

Kikuchi

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Regulations of proliferation and quiescence in response to nutritional cues are important for medicine and basic biology. The fission yeast Schizosaccharomyces pombe serves as a model, owing to the shift of proliferating cells to the metabolically active quiescence (designate G0 phase hereafter) by responding to low nitrogen source. S. pombe G0 phase cells keep alive for months without growth and division. Nitrogen replenishment reinstates vegetative proliferation phase (designate VEG). Some 40 genes required for G0 maintenance were identified, but many more remain to be identified. We here show, using mutants, that the proteasome is required for maintaining G0 quiescence. Functional outcomes of proteasome in G0 and VEG phases appear to be distinct. Upon proteasome dysfunction, a number of antioxidant proteins and compounds responsive to ROS (reactive oxygen species) are produced. In addition, autophagy-mediated destruction of mitochondria occurs, which suppresses the loss of viability by eliminating ROS-generating mitochondria. These defensive responses are found in G0 but not in VEG, suggesting that the main function of proteasome in G0 phase homeostasis is to minimize ROS. Proteasome and autophagy are thus collaborative to support the lifespan of S. pombe G0 phase.cell cycle | cellular quiescence | proteolysis | mitochondria

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Section: Resultsmentioning

confidence: 99%

Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast

Takeda

Yoshida

Kikuchi

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Therefore, HDACs themselves are not involved in neutral lipid metabolism directly and SIR2 stimulates the accumulation of neutral lipids when cells were cultured with VPA. Recently, Zhang et al [26] reported that cells defective in TAG synthesis undergo apoptosis upon entry into the stationary phase and diacylglycerol (DAG) mediates fatty acid-induced lipoapoptosis in Schizosaccharomyces pombe. In our experiment, however, DAG and monoacylglycerol (MAG) levels of the cells cultured with or without VPA were quite low compared to TAG level analyzed by the TLC method.…”

Section: Discussionmentioning

confidence: 99%

Valproate induces apoptosis by inducing accumulation of neutral lipids which was prevented by disruption of the SIR2 gene in Saccharomyces cerevisiae

Sun

et al. 2007

FEBS Letters

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We investigated the participation of HDACs in VPA induced apoptosis in Saccharomyces cerevisiae. VPA (20 mM) induced apoptosis in several HDAC mutants, including PRD3 and HDA1-disrupted cells and SIR2 over expressing cells, as well as in wild-type cells but not SIR2-disrupted cells. Intracellular reactive oxygen species and neutral lipid content increased markedly in all kinds of HDAC mutant cells tested except for SIR2-disrupted cells. Thus, these results suggest that 20 mM VPA induces neutral lipid accumulation and apoptosis-like features in S. cerevisiae, and that VPA-induced apoptosis was evaded by deletion of SIR2.

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“…several organisms (3,46) and is likely to play a major role in the metabolic syndrome of obesity, diabetes, and atherosclerosis. We therefore investigated the mechanism of cell death in yeast acyltransferase mutants treated with oleate or palmitoleate (Fig.…”

Section: Expression Of Human Dgat2mentioning

confidence: 99%

Sterol and Diacylglycerol Acyltransferase Deficiency Triggers Fatty Acid-mediated Cell Death

Garbarino

Padamsee

Wilcox

et al. 2009

Journal of Biological Chemistry

144

157

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Deletion of the acyltransferases responsible for triglyceride and steryl ester synthesis in Saccharomyces cerevisiae serves as a genetic model of diseases where lipid overload is a component. The yeast mutants lack detectable neutral lipids and cytoplasmic lipid droplets and are strikingly sensitive to unsaturated fatty acids. Expression of human diacylglycerol acyltransferase 2 in the yeast mutants was sufficient to reverse these phenotypes. Similar to mammalian cells, fatty acid-mediated death in yeast is apoptotic and presaged by transcriptional induction of stressresponse pathways, elevated oxidative stress, and activation of the unfolded protein response. To identify pathways that protect cells from lipid excess, we performed genetic interaction and transcriptional profiling screens with the yeast acyltransferase mutants. We thus identified diacylglycerol kinase-mediated phosphatidic acid biosynthesis and production of phosphatidylcholine via methylation of phosphatidylethanolamine as modifiers of lipotoxicity. Accordingly, the combined ablation of phospholipid and triglyceride biosynthesis increased sensitivity to saturated fatty acids. Similarly, normal sphingolipid biosynthesis and vesicular transport were required for optimal growth upon denudation of triglyceride biosynthesis and also mediated resistance to exogenous fatty acids. In metazoans, many of these processes are implicated in insulin secretion thus linking lipotoxicity with early aspects of pancreatic ␤-cell dysfunction, diabetes, and the metabolic syndrome.

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Schizosaccharomyces pombe Cells Deficient in Triacylglycerols Synthesis Undergo Apoptosis upon Entry into the Stationary Phase

Cited by 119 publications

References 53 publications

Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast

Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast

Valproate induces apoptosis by inducing accumulation of neutral lipids which was prevented by disruption of the SIR2 gene in Saccharomyces cerevisiae

Sterol and Diacylglycerol Acyltransferase Deficiency Triggers Fatty Acid-mediated Cell Death

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