Coordinated regulation of sulfur and phospholipid metabolism reflects the importance of methylation in the growth of yeast

Hickman, Mark J.; Petti, Allegra A.; Ho-Shing, Olivia; Silverman, Sanford J.; McIsaac, R. Scott; Lee, Traci A.; Botstein, David

doi:10.1091/mbc.e11-05-0467

Cited by 44 publications

(53 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, transcription of these genes was also repressed by methionine (Figure 3B). Our observations on the transcriptional coordination between phospholipid synthesis and sulfur metabolism are consistent with previous reports (Hickman et al, 2011; Sadhu et al, 2014). …”

Section: Resultssupporting

confidence: 93%

“…The findings that PE methylation regulates plasma homocysteine and the excretion levels of homocysteine from hepatocytes (Vance, 2014) implicate a function for PE methylation in sulfur metabolism. Moreover, studies in yeast have linked the synthesis of phospholipids to the transcriptional regulation of sulfur metabolic genes (Hickman et al, 2011; Sadhu et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Metabolic Function for Phospholipid and Histone Methylation

et al. 2017

View full text Add to dashboard Cite

SUMMARY S-adenosylmethionine (SAM) is the methyl donor for biological methylation modifications that regulate protein and nucleic acid functions. Here we show that methylation of a phospholipid, phosphatidylethanolamine (PE), is a major consumer of SAM. The induction of phospholipid biosynthetic genes is accompanied by induction of the enzyme that hydrolyzes S-adenosylhomocysteine (SAH), a product and inhibitor of methyltransferases. Beyond its function for the synthesis of phosphatidylcholine (PC), the methylation of PE facilitates the turnover of SAM for the synthesis of cysteine and glutathione through transsulfuration. Strikingly, cells that lack PE methylation accumulate SAM, which leads to hypermethylation of histones and the major phosphatase PP2A, dependency on cysteine, and sensitivity to oxidative stress. Without PE methylation, particular sites on histones then become methyl sinks to enable the conversion of SAM to SAH. These findings reveal an unforeseen metabolic function for phospholipid and histone methylation intrinsic to the life of a cell.

show abstract

Section: Resultssupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

A Metabolic Function for Phospholipid and Histone Methylation

et al. 2017

View full text Add to dashboard Cite

show abstract

“…A recent study showed that met4 Δ mutants grow poorly even when supplemented with methionine. However, the addition of SAM restored normal growth rates, suggesting that SAM levels are rate-limiting for supporting maximal growth rates (Hickman et al, 2011). Lastly, ~1% of yeast and mammalian gene products encode SAM-dependent methyltransferases (Petrossian and Clarke, 2011), and this number does not include enzymes that utilize SAM via other mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Methionine Inhibits Autophagy and Promotes Growth by Inducing the SAM-Responsive Methylation of PP2A

Sutter

Laxman

et al. 2013

Cell

211

260

View full text Add to dashboard Cite

Summary Autophagy is a process of cellular self-digestion induced by various forms of starvation. The mechanisms by which metabolic deficiencies are sensed by a cell to regulate autophagy remain unclear. While nitrogen deficit is a common trigger, yeast cells induce autophagy upon switch from a rich to minimal media without nitrogen starvation. We show that the amino acid methionine is sufficient to inhibit such non-nitrogen starvation (NNS)-induced autophagy. Methionine boosts synthesis of the methyl donor, S-adenosylmethionine (SAM). SAM inhibits autophagy and promotes growth through the action of the methyltransferase Ppm1p, which methylates the catalytic subunit of PP2A in tune with SAM levels. Methylated PP2A promotes dephosphorylation of Npr2p, a component of a conserved complex that regulates NNS-autophagy and other growth-related processes. Thus, methionine and SAM levels represent a critical gauge of amino acid availability that is sensed via this distinctive methylation modification of PP2A to reciprocally regulate cell growth and autophagy.

show abstract

“…Binding of Cbf1 to upstream sites is required for binding of the ISW2 chromatin-remodeling complex, which is also required for full INO1 derepression (Shetty and Lopes, 2010). Cbf1p also interacts with Met4p, a transcriptional activator in the sulfur assimilation pathway, which is required for activation of genes, including SAM1 and SAM2 , described above, which are required for maintaining levels of Sadenosyl methionine (SAM) (Hickman et al, 2011; Petti et al, 2012), the methyl donor in the phospholipid methylation reactions catalyzed by Cho2p and Opi3p in the synthesis of PC from PE (Fig. 1).…”

Section: Biosynthesis Of Inositol In S Cerevisiae: Biochemistry mentioning

confidence: 99%

“…1). Whereas Met4p is required for SAM2 activation, Opi1p is a direct repressor of SAM2 (Hickman et al, 2011). …”

Section: Biosynthesis Of Inositol In S Cerevisiae: Biochemistry mentioning

confidence: 99%

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

Henry

Gaspar

Jesch

2014

Chemistry and Physics of Lipids

100

View full text Add to dashboard Cite

This article focuses on discoveries of the mechanisms governing the regulation of glycerolipid metabolism and stress response signaling in response to the phospholipid precursor, inositol. The regulation of glycerolipid lipid metabolism in yeast in response to inositol is highly complex, but increasingly well understood, and the roles of individual lipids in stress response are also increasingly well characterized. Discoveries that have emerged over several decades of genetic, molecular and biochemical analyses of metabolic, regulatory and signaling responses of yeast cells, both mutant and wild type, to the availability of the phospholipid precursor, inositol are discussed.

show abstract

Coordinated regulation of sulfur and phospholipid metabolism reflects the importance of methylation in the growth of yeast

Cited by 44 publications

References 65 publications

A Metabolic Function for Phospholipid and Histone Methylation

A Metabolic Function for Phospholipid and Histone Methylation

Methionine Inhibits Autophagy and Promotes Growth by Inducing the SAM-Responsive Methylation of PP2A

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

Contact Info

Product

Resources

About