Stress-Induced Cell Death Is Mediated by Ceramide Synthesis in
            <i>Neurospora crassa</i>

Plesofsky, Nora; Levery, Steven B.; Castle, Sherry A.; Brambl, Robert

doi:10.1128/ec.00147-08

Cited by 26 publications

(34 citation statements)

References 82 publications

(90 reference statements)

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“…The inducible strain PB20i had a very similar viability to the lac‐1 KO bd strain previously analyzed (Tables 2 and 5), confirming the viability effect of the double mutant, but induction of lac‐1 + shortened the estimated median chronological lifespan to just 7.5 days. While there may be other explanations for this sharp decrease in viability, such as interference between the induced lac‐1 + transcript and other transcriptional units, there is interesting evidence that the expression of ceramide synthases, such as lag‐1 or lac‐1 , and the level of phytoceramide production may have been optimized by natural selection to a specific level over time, and any other level of ceramide production may be deleterious (Plesofsky et al., 2008) (Jiang et al., 2004). …”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have suggested that phytoceramide is expressed at an optimum level within the conidia of N. crassa (Plesofsky et al., 2008). We predict that the optimum level of phytoceramide production shifts based on the activity of phytoceramide‐producing genes.…”

Section: Resultsmentioning

confidence: 99%

“…We used a protocol we have modified from a previous study on ceramide stress signaling in N. crassa (Plesofsky et al., 2008). We have modified the protocol to test conidial response to an increasing gradient of phytoceramide in WT, lag‐1 KO bd (MC31), and lac‐1 KO bd (PB42) strains of N. crassa grown in liquid culture.…”

Section: Methodsmentioning

confidence: 99%

“…Phytoceramide is one of the two major classes of ceramides found from fungal populations; the other class includes the monohexose‐modified ceramides (Merrill, 2002) (Warnecke & Heinz, 2003). Phytoceramide has been demonstrated to play an important role in mediating and possibly decreasing instances of stress‐induced cell death, but the decrease in stress‐related cell death only occurs at specific dosages, beyond which phytoceramide can have a lethal effect (Plesofsky, Levery, Castle, & Brambl, 2008). This is partial evidence for balancing selection on a quantitative trait, namely the level of phytoceramide synthesis.…”

Section: Introductionmentioning

confidence: 99%

“…They are not dormant. The internal physiological deterioration of conidia under stress has been linked to the apoptotic signal of phytoceramides in N. crassa , a metabolic product of lac‐1 (Plesofsky et al., 2008). We will measure a fitness component through viability curves.…”

Section: Introductionmentioning

confidence: 99%

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lac‐1 and lag‐1 with ras‐1 affect aging and the biological clock in Neurospora crassa

Brunson

Griffith

Bowles

et al. 2016

Ecology and Evolution

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Using an automated cell counting technique developed previously (Case et al., Ecology and Evolution 2014; 4: 3494), we explore the lifespan effects of lac‐1, a ceramide synthase gene paralogous to lag‐1 in Neurospora crassa in conjunction with the band bd (ras‐1) gene. We find that the replicative lifespan of a lac‐1 KO bd double mutants is short, about one race tube cycle, and this double mutant lacks a strong ~21‐hr clock cycle as shown by race tube and fluorometer analysis of fluorescent strains including lac‐1 KO. This short replicative lifespan phenotype is contrasted with a very long estimated chronological lifespan for lac‐1 KO bd double mutants from 247 to 462 days based on our regression analyses on log viability, and for the single mutant lac‐1 KO, 161 days. Both of these estimated lifespans are much higher than that of previously studied WT and bd single mutant strains. In a lac‐1 rescue and induction experiment, the expression of lac‐1 + as driven by a quinic acid‐dependent promoter actually decreases the median chronological lifespan of cells down to only 7 days, much lower than the 34‐day median lifespan found in control bd conidia also grown on quinic acid media, which we interpret as an effect of balancing selection acting on ceramide levels based on previous findings from the literature. Prior work has shown phytoceramides can act as a signal for apoptosis in stressed N. crassa cells. To test this hypothesis of balancing selection on phytoceramide levels, we examine the viability of WT, lag‐1 KO bd, and lac‐1 KO bd strains following the dual stresses of heat and glycolysis inhibition, along with phytoceramide treatments of different dosages. We find that the phytoceramide dosage–response curve is altered in the lag‐1 KO bd mutant, but not in the lac‐1 KO bd mutant. We conclude that phytoceramide production is responsible for the previously reported longevity effects in the lag‐1 KO bd mutant, but a different ceramide may be responsible for the longevity effect observed in the lac‐1 KO bd mutant.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

lac‐1 and lag‐1 with ras‐1 affect aging and the biological clock in Neurospora crassa

Brunson

Griffith

Bowles

et al. 2016

Ecology and Evolution

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Sphingolipid‐enriched domains in fungi

et al. 2020

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Plasma membrane carries out multiple physiological functions that require its dynamic and tightly regulated organization into specialized domains of different size, stability, and lipid/protein composition. Sphingolipids are a group of lipids in which the plasma membrane is particularly enriched, thus being crucial for its structure and function. A specific type of sphingolipid‐enriched plasma membrane domains, where ergosterol is depleted and lipids are tightly packed in a rigid gel phase, has recently been found in several fungal species, including yeasts and moulds. After presenting the main biophysical features of gel domains and the experimental method for their detection in the fungal plasma membrane, we review these sphingolipid‐enriched gel domains and illustrate their importance to both unicellular and multicellular fungi. First, the biophysical properties of the fungal sphingolipid‐enriched domains will be analysed taking into consideration the plasma membrane sphingolipidome. Next, their possible biological roles will be summarized, including their relations with plasma membrane compartments and involvement in stress responses. Moreover, since the plasma membrane is a target for several antifungal compounds, a biophysical connection between sphingolipid‐enriched domains and antifungal action will be explored.

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