Starvation for an essential amino acid induces apoptosis and oxidative stress in yeast

Eisler, Herfried; Fröhlich, Kai‐Uwe; Heidenreich, Erich

doi:10.1016/j.yexcr.2004.07.025

Cited by 65 publications

(45 citation statements)

References 41 publications

(61 reference statements)

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“…Upon PHS treatment, wild type cells initiated a massive production of ROS with a maximum at about 80 min. ROS production preceded DNA fragmentation, which was only detected some hours later, in agreement with evidence that ROS accumulation precedes the onset of apoptosis (56). In sharp contrast, fewer ROS were generated by the complex I mutants under the same conditions.…”

Section: Discussionsupporting

confidence: 85%

Increased Resistance of Complex I Mutants to Phytosphingosine-induced Programmed Cell Death

Castro

Lemos

Falcão

et al. 2008

Journal of Biological Chemistry

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We have studied the effects of phytosphingosine (PHS) on cells of the filamentous fungus Neurospora crassa. Highly reduced viability, impairment of asexual spore germination, DNA condensation and fragmentation, and production of reactive oxygen species were observed in conidia treated with the drug, suggesting that PHS induces an apoptosis-like death in this fungus. Interestingly, we found that complex I mutants are more resistant to PHS treatment than the wild type strain. This effect appears to be specific because it was not observed in mutants defective in other components of the mitochondrial respiratory chain, pointing to a particular involvement of complex I in cell death. The response of the mutant strains to PHS correlated with their response to hydrogen peroxide. The fact that complex I mutants generate fewer reactive oxygen species than the wild type strain when exposed to PHS likely explains the PHS-resistant phenotype. As compared with the wild type strain, we also found that a strain containing a deletion in the gene encoding an AIF (apoptosis-inducing factor)-like protein is more resistant to PHS and H 2 O 2 . In contrast, a strain containing a deletion in a gene encoding an AMID (AIF-homologous mitochondrion-associated inducer of death)-like polypeptide is more sensitive to both drugs. These results indicate that N. crassa has the potential to be a model organism to investigate the molecular basis of programmed cell death in eukaryotic species.

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Section: Discussionsupporting

confidence: 85%

Increased Resistance of Complex I Mutants to Phytosphingosine-induced Programmed Cell Death

Castro

Lemos

Falcão

et al. 2008

Journal of Biological Chemistry

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“…ROS species have the potential to induce cell death in yeast (Eisler et al, 2004;Klassen and Meinhardt, 2005;Laun et al, 2001;Ludovico et al, 2001;Madeo et al, 1999). Dihydrorhodamine 123 is a reliable indicator for ROS, as it is rapidly converted into a highly fluorescent derivative upon interacting with ROS.…”

Section: Characterization Of Cell Death Caused By Laaomentioning

confidence: 99%

“…This may be attributed to the different insults acting upon the cells at the same time and which could trigger more cells to undergo apoptotic cell death. We have reported that the depletion of an essential amino acid can trigger apoptotic cell death in yeast (Eisler et al, 2004). Other members of the LAAO family, such as achacin from the body surface mucus of the giant African snail (Achatina fulica Ferussac) and the apoptosis-inducing protein (AIP) from parasiteinfected fish, deplete arginine, lysine, tryptophan and tyrosine, or only lysine, from mammalian cell culture medium (Kanzawa et al, 2004;Murakawa in the presence of catalase (1.5 µM) for 30 min.…”

Section: Interaction Of Laao With the Yeast Cellmentioning

confidence: 99%

“…Very surprisingly, apoptotic markers were also observed in yeast in association with the mutation in the AAA-ATPase gene CDC48, leading to the discovery of apoptotic processes in unicellular eukaryotes (Madeo et al, 1997). In recent years, several factors that induce apoptosis have been discovered, such as acetic acid (Ludovico et al, 2001), depletion of essential amino acids (Eisler et al, 2004), ageing (Laun et al, 2001) and the yeast killer toxin from Pichia acaciae (Klassen and Meinhardt, 2005). In all these cases the reactive oxygen species (ROS) generated inside the cell played an important role in inducing apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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Induction of apoptosis in yeast by L‐amino acid oxidase from the Malayan pit viper Calloselasma rhodostoma

Ande

Fussi

Knauer

et al. 2008

Yeast

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Here we report for the first time that L-amino acid oxidase (LAAO), a major component of snake venom, induces apoptosis in yeast. The causative agent for induction of apoptosis has been shown to be hydrogen peroxide, produced by the enzymatic activity of LAAO. However, the addition of catalase, a specific hydrogen peroxide scavenger, does not prevent cell demise completely. Intriguingly, depletion of leucine from the medium by LAAO and the interaction of LAAO with yeast cells are shown to be the major factors responsible for cell demise in the presence of catalase.

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“…Seven enzymes, eight steps, and more than 12 unlinked genes are responsible for the biosynthesis of lysine in S. cerevisiae. This amino acid, which is preferentially located in the vacuole, and cannot be used as nitrogen or carbon source (Watson, 1976), plays an important physiological role, contributing to the build-up of the stress response provoked by H 2 O 2 treatment (Stephen & Jamieson, 1997), prevention of amino acid starvation-induced apoptosis (Eisler et al, 2004), and cryoprotection (Takagi et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Specialization of the paralogue LYS21 determines lysine biosynthesis under respiratory metabolism in Saccharomyces cerevisiae

et al. 2008

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In the yeast Saccharomyces cerevisiae, the first committed step of the lysine biosynthetic pathway is catalysed by two homocitrate synthases encoded by LYS20 and LYS21. We undertook a study of the duplicate homocitrate synthases to analyse whether their retention and presumable specialization have affected the efficiency of lysine biosynthesis in yeast. Our results show that during growth on ethanol, homocitrate is mainly synthesized through Lys21p, while under fermentative metabolism, Lys20p and Lys21p play redundant roles. Furthermore, results presented in this paper indicate that, in contrast to that which had been found for Lys20p, lysine is a strong allosteric inhibitor of Lys21p (K i 0.053 mM), which, in addition, induces positive cooperativity for a-ketoglutarate (a-KG) binding. Differential lysine inhibition and modulation by a-KG of the two isozymes, and the regulation of the intracellular amount of the two isoforms, give rise to an exquisite regulatory system, which balances the rate at which a-KG is diverted to lysine biosynthesis or to other metabolic pathways. It can thus be concluded that retention and further biochemical specialization of the LYS20-and LYS21-encoded enzymes with partially overlapping roles contributed to the acquisition of facultative metabolism.

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Starvation for an essential amino acid induces apoptosis and oxidative stress in yeast

Cited by 65 publications

References 41 publications

Increased Resistance of Complex I Mutants to Phytosphingosine-induced Programmed Cell Death

Increased Resistance of Complex I Mutants to Phytosphingosine-induced Programmed Cell Death

Induction of apoptosis in yeast by L‐amino acid oxidase from the Malayan pit viper Calloselasma rhodostoma

Specialization of the paralogue LYS21 determines lysine biosynthesis under respiratory metabolism in Saccharomyces cerevisiae

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