ArticleThe Journal of biological chemistry2012
Sphingoid bases and the serine catabolic enzyme CHA1 define a novel feedforward/feedback mechanism in the response to serine availability.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 25 citations in OpenAlex.
- Uptake of exogenous serine is important to maintain sphingolipid homeostasis in Saccharomyces cerevisiae.PLoS genetics · 2020Article
- Protection mechanisms against aberrant metabolism of sphingolipids in budding yeast.Current genetics · 2018Review
- Membrane engineering of S. cerevisiae targeting sphingolipid metabolism.Scientific reports · 2017Article
- Following the flux of long-chain bases through the sphingolipid pathway in vivo using mass spectrometry.Journal of lipid research · 2016Article
- 1-Deoxysphingolipids Encountered Exogenously and Made de Novo: Dangerous Mysteries inside an Enigma.The Journal of biological chemistry · 2015Review
- Sphingolipids and mitochondrial function in budding yeast.Biochimica et biophysica acta · 2014Article
- The yeast sphingolipid signaling landscape.Chemistry and physics of lipids · 2014Review
- Distinct signaling roles of ceramide species in yeast revealed through systematic perturbation and systems biology analyses.Science signaling · 2013Article
- Sphingolipid homeostasis in the endoplasmic reticulum and beyond.Cold Spring Harbor perspectives in biology · 2013Review
- Iron, glucose and intrinsic factors alter sphingolipid composition as yeast cells enter stationary phase.Biochimica et biophysica acta · 2013Article
- Modulation of mitochondrial outer membrane permeabilization and apoptosis by ceramide metabolism.PloS one · 2012Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Targets of bioactive sphingolipids in Saccharomyces cerevisiae were previously identified using microarray experiments focused on sphingolipid-dependent responses to heat stress. One of these heat-induced genes is the serine deamidase/dehydratase Cha1 known to be regulated by increased serine availability. This study investigated the hypothesis that sphingolipids may mediate the induction of Cha1 in response to serine availability. The results showed that inhibition of de novo synthesis of sphingolipids, pharmacologically or genetically, prevented the induction of Cha1 in response to increased serine availability. Additional studies implicated the sphingoid bases phytosphingosine and dihydrosphingosine as the likely mediators of Cha1 up-regulation. The yeast protein kinases Pkh1 and Pkh2, known sphingoid base effectors, were found to mediate CHA1 up-regulation via the transcription factor Cha4. Because the results disclosed a role for sphingolipids in negative feedback regulation of serine metabolism, we investigated the effects of disrupting this mechanism on sphingolipid levels and on cell growth. Intriguingly, exposure of the cha1Δ strain to high serine resulted in hyperaccumulation of endogenous serine and in turn a significant accumulation of sphingoid bases and ceramides. Under these conditions, the cha1Δ strain displayed a significant growth defect that was sphingolipid-dependent. Together, this work reveals a feedforward/feedback loop whereby the sphingoid bases serve as sensors of serine availability and mediate up-regulation of Cha1 in response to serine availability, which in turn regulates sphingolipid levels by limiting serine accumulation.
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Registered trials
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