Opi1 mediates repression of phospholipid biosynthesis by phosphate limitation in the yeast<i>Saccharomyces cerevisiae</i>

Kliewe, Felix; Kumme, Jacqueline; Grigat, Mathias; Hintze, Stefan; Schüller, Hans‐Joachim

doi:10.1002/yea.3215

Cited by 7 publications

(8 citation statements)

References 44 publications

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“…2007; Lee et al . 2008; Kliewe et al . 2017a), this observation might give new insights for further exploration of these pathways.…”

Section: Discussionmentioning

confidence: 99%

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Opi1-mediated transcriptional modulation orchestrates genotoxic stress response in budding yeast

Panessa

Pires

et al. 2022

Preprint

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Inositol is a six-carbon sugar that functions as a precursor for signaling molecules such as phosphoinositides and inositol polyphosphates, which are involved in the regulation of important biological processes such as energy metabolism, environmental stress response, phosphate signaling, among others. Given its role in a myriad of signaling pathways, regulation of inositol synthesis is essential for cellular homeostasis. In budding yeast, transcription of genes involved in inositol metabolism is regulated by the transcriptional repressor Opi1, which repress transcription of genes containing cis-acting inositol-sensitive upstream activation sequences (UASINO). Upon genotoxic stress, cells activate the DNA Damage Response (DDR) to coordinate DNA repair and cell cycle progression. It has been proposed that inositol containing molecules might act as modulators of the DDR, but evidences are still scarce. Herein, we report thatopi1cells fail to downregulate the inositol phosphate pathway leading to sensitivity to genotoxins and replication defects. Moreover, cells lacking Opi1 show decreased gamma-H2A levels which might indicate that Opi1 contributes to the activation of the DDR kinases Mec1/Tel1 (ATR/ATM in mammals). Importantly, we show that deletion of the inositol pyrophosphate kinase Kcs1 (IP6K1/2/3 in mammals), which leads to inhibition of inositol pyrophosphate synthesis, rescues the MMS sensitivity and replication defects ofopi1cells. Further, overexpression of Kcs1 recapitulates the MMS sensitivity of cells lacking Opi1. Therefore, we propose that cells must downregulate inositol pyrophosphate synthesis during replication stress in order to trigger an effective DNA Damage Response.

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“…2007; Lee et al . 2008; Kliewe et al . 2017a), this observation might give new insights for further exploration of these pathways.…”

Section: Discussionmentioning

confidence: 99%

“…Figure 4). Because inositol and phosphate metabolism are intimately related (Auesukaree et al 2005;Mulugu et al 2007;Lee et al 2008;Kliewe et al 2017a), this observation might give new insights for further exploration of these pathways.…”

Section: Pp-ips Overproduction Affects the Response To Replication St...mentioning

confidence: 92%

Opi1-mediated transcriptional modulation orchestrates genotoxic stress response in budding yeast

Panessa

Pires

et al. 2022

Preprint

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“…The interaction between Scs2 and Opi1 favors binding of the transcriptional regulator to phosphatidic acid (PA) at the nuclear membrane and expression of lipid biosynthetic genes. Conditions that result in PA consumption favor the release of Opi1 from the ONM, allowing its translocation to the nucleus and subsequent repression of its target genes (Kliewe et al, 2017). Investigating a link between Scs2 and Mps3 could connect lipid homeostasis at the ONM with telomere silencing at the INM through known functions of Mps3, Scs2 or both.…”

Section: Mps3 and Lipid Metabolismmentioning

confidence: 99%

SUNny Ways: The Role of the SUN-Domain Protein Mps3 Bridging Yeast Nuclear Organization and Lipid Homeostasis

Ponce

Moradi-Fard²,

Zaremberg

et al. 2020

Front. Genet.

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Mps3 is a SUN (Sad1-UNC-84) domain-containing protein that is located in the inner nuclear membrane (INM). Genetic screens with multiple Mps3 mutants have suggested that distinct regions of Mps3 function in relative isolation and underscore the broad involvement of Mps3 in multiple pathways including mitotic spindle formation, telomere maintenance, and lipid metabolism. These pathways have largely been characterized in isolation, without a holistic consideration for how key regulatory events within one pathway might impinge on other aspects of biology at the nuclear membrane. Mps3 is uniquely positioned to function in these multiple pathways as its N-terminus is in the nucleoplasm, where it is important for telomere anchoring at the nuclear periphery, and its C-terminus is in the lumen, where it has links with lipid metabolic processes. Emerging work suggests that the role of Mps3 in nuclear organization and lipid homeostasis are not independent, but more connected. For example, a failure in regulating Mps3 levels through the cell cycle leads to nuclear morphological abnormalities and loss of viability, suggesting a link between the N-terminal domain of Mps3 and nuclear envelope homeostasis. We will highlight work suggesting that Mps3 is pivotal factor in communicating events between the nucleus and the lipid bilayer.

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“…The latter relates to a negative effect of Pah1 on the transcription of several V-ATPase subunit genes, which all contain an UAS INO element in their promotor 206 . This is interesting since this promotor element also links the expression of these V-ATPase genes to phospholipid biosynthesis and the availability of inositol, choline and phosphate 208 .…”

Section: Ph Control Stress Tolerance and Longevitymentioning

confidence: 99%

pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity

Deprez¹,

Eskes²,

Wilms³

et al. 2018

Microb Cell

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The plasma membrane H+-ATPase Pma1 and the vacuolar V-ATPase act in close harmony to tightly control pH homeostasis, which is essential for a vast number of physiological processes. As these main two regulators of pH are responsive to the nutritional status of the cell, it seems evident that pH homeostasis acts in conjunction with nutrient-induced signalling pathways. Indeed, both PKA and the TORC1-Sch9 axis influence the proton pumping activity of the V-ATPase and possibly also of Pma1. In addition, it recently became clear that the proton acts as a second messenger to signal glucose availability via the V-ATPase to PKA and TORC1-Sch9. Given the prominent role of nutrient signalling in longevity, it is not surprising that pH homeostasis has been linked to ageing and longevity as well. A first indication is provided by acetic acid, whose uptake by the cell induces toxicity and affects longevity. Secondly, vacuolar acidity has been linked to autophagic processes, including mitophagy. In agreement with this, a decline in vacuolar acidity was shown to induce mitochondrial dysfunction and shorten lifespan. In addition, the asymmetric inheritance of Pma1 has been associated with replicative ageing and this again links to repercussions on vacuolar pH. Taken together, accumulating evidence indicates that pH homeostasis plays a prominent role in the determination of ageing and longevity, thereby providing new perspectives and avenues to explore the underlying molecular mechanisms.

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Opi1 mediates repression of phospholipid biosynthesis by phosphate limitation in the yeastSaccharomyces cerevisiae

Cited by 7 publications

References 44 publications

Opi1-mediated transcriptional modulation orchestrates genotoxic stress response in budding yeast

Opi1-mediated transcriptional modulation orchestrates genotoxic stress response in budding yeast

SUNny Ways: The Role of the SUN-Domain Protein Mps3 Bridging Yeast Nuclear Organization and Lipid Homeostasis

pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity

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