The response to inositol: Regulation of glycerolipid metabolism and stress response signaling in yeast

Henry, Susan A.; Gaspar, María L.; Jesch, Stephen A.

doi:10.1016/j.chemphyslip.2013.12.013

Cited by 81 publications

(99 citation statements)

References 275 publications

(486 reference statements)

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“…1) [41]. PI(4,5)P 2 is a relatively common phospholipid, that plays key regulatory roles in a number of essential cellular processes [29,64], including ion channel modulation [101], cytoskeletal regulation [88,112], endocytosis of plasma membrane proteins [103] and membrane identity [38].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Characterization of the S. cerevisiae inp51 mutant links phosphatidylinositol 4,5-bisphosphate levels with lipid content, membrane fluidity and cold growth

Córcoles-Sáez

Hernández

Martínez-Rivas

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Section: Accepted Manuscriptmentioning

confidence: 99%

Characterization of the S. cerevisiae inp51 mutant links phosphatidylinositol 4,5-bisphosphate levels with lipid content, membrane fluidity and cold growth

Córcoles-Sáez

Hernández

Martínez-Rivas

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…It is unclear, however, why fungi would accumulate TAG during symbiosis establishment, when a more plausible progression would be to break down TAG to release the energy source for bacteria. An alternative explanation is that the accumulation of TAG and PE during symbiosis establishment could be a result of transient accumulation of their precursor PA. PA is known to have signaling roles in eukaryotes (18) and it is possible that an accumulation of PA, undetected in this study, serves a signaling function in the coordination of symbiosis establishment. Accumulation of TAG and PE could thus be the end result of transient accumulation of PA, which, upon serving its signaling function, could become converted into PE through the cytidine diphosphate (CDP)-DAG pathway and channeled into biosynthesis of TAG by first becoming converted into DAG via a PA phosphatase.…”

Section: Hog-mediated Activation Of Lipid Metabolism During Symbiosismentioning

confidence: 99%

“…1). Central intermediates of this pathway are diacylglycerol (17,18). They are interconvertible, i.e., PA can be dephosphorylated by a PA phosphatase to produce DAG (19), and DAG can be phosphorylated by DAG kinase (DGK) to yield PA (20).…”

Section: Up-regulation Of Genes Responsible For the Hog Pathway And Lmentioning

confidence: 99%

Lipid metabolic changes in an early divergent fungus govern the establishment of a mutualistic symbiosis with endobacteria

Lastovetsky

Gaspar

Mondo

et al. 2016

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

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The recent accumulation of newly discovered fungal-bacterial mutualisms challenges the paradigm that fungi and bacteria are natural antagonists. To understand the mechanisms that govern the establishment and maintenance over evolutionary time of mutualisms between fungi and bacteria, we studied a symbiosis of the fungus Rhizopus microsporus (Mucoromycotina) and its Burkholderia endobacteria. We found that nonhost R. microsporus, as well as other mucoralean fungi, interact antagonistically with endobacteria derived from the host and are not invaded by them. Comparison of gene expression profiles of host and nonhost fungi during interaction with endobacteria revealed dramatic changes in expression of lipid metabolic genes in the host. Analysis of the host lipidome confirmed that symbiosis establishment was accompanied by specific changes in the fungal lipid profile. Diacylglycerol kinase (DGK) activity was important for these lipid metabolic changes, as its inhibition altered the fungal lipid profile and caused a shift in the host-bacterial interaction into an antagonism. We conclude that adjustments in host lipid metabolism during symbiosis establishment, mediated by DGKs, are required for the mutualistic outcome of the Rhizopus-Burkholderia symbiosis. In addition, the neutral and phospholipid profiles of R. microsporus provide important insights into lipid metabolism in an understudied group of oleaginous Mucoromycotina. Lastly, our study revealed that the DGKs involved in the symbiosis form a previously uncharacterized clade of DGK domain proteins. mutualism evolution | antagonism | Mucoromycotina | oleaginous fungi |

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“…2, A and B) and is suppressed by mutations in the CDP-choline pathway for PC biosynthesis (17,18). The opi1⌬ mutation, in contrast, confers constitutive overexpression of INO1 and other UAS INO -containing genes (3)(4)(5)33), resulting in overproduction and excretion of inositol into the growth medium (Opi Ϫ phenotype). The opi1⌬ mutant also exhibits a Pet Ϫ phenotype (i.e.…”

mentioning

confidence: 99%

Interaction between repressor Opi1p and ER membrane protein Scs2p facilitates transit of phosphatidic acid from the ER to mitochondria and is essential for INO1 gene expression in the presence of choline

Gaspar¹,

Chang²,

Jesch

et al. 2017

Journal of Biological Chemistry

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In the yeast Saccharomyces cerevisiae, the Opi1p repressor controls the expression of INO1 via the Opi1p/Ino2p-Ino4p regulatory circuit. Inositol depletion favors Opi1p interaction with both Scs2p and phosphatidic acid at the endoplasmic reticulum (ER) membrane. Inositol supplementation, however, favors the translocation of Opi1p from the ER into the nucleus, where it interacts with the Ino2p-Ino4p complex, attenuating transcription of INO1. A strain devoid of Scs2p (scs2⌬) and a mutant, OPI1FFAT, lacking the ability to interact with Scs2p were utilized to examine the specific role(s) of the Opi1p-Scs2p interaction in the regulation of INO1 expression and overall lipid metabolism. Loss of the Opi1p-Scs2p interaction reduced INO1 expression and conferred inositol auxotrophy. Moreover, inositol depletion in strains lacking this interaction resulted in Opi1p being localized to sites of lipid droplet formation, coincident with increased synthesis of triacylglycerol. Supplementation of choline to inositol-depleted growth medium led to decreased TAG synthesis in all three strains. However, in strains lacking the Opi1p-Scs2p interaction, Opi1p remained in the nucleus, preventing expression of INO1. These data support the conclusion that a specific pool of phosphatidic acid, associated with lipid droplet formation in the perinuclear ER, is responsible for the initial rapid exit of Opi1p from the nucleus to the ER and is required for INO1 expression in the presence of choline. Moreover, the mitochondria-specific phospholipid, cardiolipin, was significantly reduced in both strains compromised for Opi1p-Scs2p interaction, indicating that this interaction is required for the transfer of phosphatidic acid from the ER to the mitochondria for cardiolipin synthesis.

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The response to inositol: Regulation of glycerolipid metabolism and stress response signaling in yeast

Cited by 81 publications

References 275 publications

Characterization of the S. cerevisiae inp51 mutant links phosphatidylinositol 4,5-bisphosphate levels with lipid content, membrane fluidity and cold growth

Characterization of the S. cerevisiae inp51 mutant links phosphatidylinositol 4,5-bisphosphate levels with lipid content, membrane fluidity and cold growth

Lipid metabolic changes in an early divergent fungus govern the establishment of a mutualistic symbiosis with endobacteria

Interaction between repressor Opi1p and ER membrane protein Scs2p facilitates transit of phosphatidic acid from the ER to mitochondria and is essential for INO1 gene expression in the presence of choline

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