A comparison of the aging and apoptotic transcriptome of

Abstract

In this paper, we present the results of global transcript analysis by the microarray technique of senescent and apoptotic yeast cells. We compared young daughter and old mother cells isolated by elutriation centrifugation, and non-apoptotic and apoptotic cells induced either by a temperature shift of the cdc48(S565G) temperature-sensitive mutant or of the orc2-1 temperature-sensitive mutant. The majority of all genes found to be differentially regulated in these three physiological situations was upregulated, indicating that a cellular death process was initiated rather than an unspecific shut-down of gene expression due to immediate killing. The functional classes of genes upregulated in all three conditions were largely the same, although individual genes were in many cases not identical. The largest group of genes involved were nuclear genes coding for mitochondrial components or functions, which is understandable given the fact that apoptosis can be triggered by mitochondrially generated oxygen radicals and that mitochondria play an important role in the execution of apoptosis. Other functional classes consisted of genes involved in DNA damage response, in cell cycle regulation and checkpoints, in DNA repair, and in membrane lipid and cell wall synthesis. These functional classes represent the response of the cell to the known cellular insults, which occur during aging and apoptosis. As we have shown previously, final-stage senescent yeast mother cells (of the wild-type) are apoptotic.

Isc1p Plays a Key Role in Hydrogen Peroxide Resistance and Chronological Lifespan through Modulation of Iron Levels and Apoptosis

“…Yca1p exhibits proteolytic activity analogous to mammalian caspases, key proteases in the execution phase of apoptosis, and is activated by oxidative stress and aging (Madeo et al, 2002). During replicative aging and in apoptotic cells, a core of genes commonly induced includes five genes in the sphingolipid metabolism functional category (Laun et al, 2005). This is consistent with an unbalance in sphingolipid levels being a causing factor of apoptosis.…”

“…The Lag1 ceramide synthase plays a key role in replicative longevity by modulating metabolism and stress resistance (Jiang et al, 2004). The LAG1 as well as other genes associated with sphingolipid metabolism, namely YPC1, YSR3, LCB5, and IPT1, are differentially expressed in aged and apoptotic cells (Laun et al, 2005). In addition, the ipt1⌬ mutants lack M(IP) 2 C and are more resistant to oxidative stress and have an increased chronological lifespan, whereas yeast mutants with increased levels of M(IP) 2 C are hypersensitive to oxidative stress and display a shorter lifespan (Aerts et al, 2006).…”

Transcriptional analysis of the response of Neurospora crassa to phytosphingosine reveals links to mitochondrial function

“…Among this set of genes, we found enrichment for genes encoding proteins belonging to functional categories that have been described to participate in stress and death responses (Bonawitz et al, 2006;Fedorova et al, 2005;Fröhlich et al, 2007;Hamann et al, 2008;Laun et al, 2005;Lu, 2006;Lucau-Danila et al, 2005). For instance, genes encoding proteins predicted to be involved in cell rescue and stress response, cell cycle and DNA processing, protein fate and modulation and for those involved in protein degradation were significantly enriched.…”

“…Much less explored has been the analysis of gene expression during the death process (Fedorova et al, 2005;Laun et al, 2005). However, it is becoming increasingly clear that PCD may involve complex metabolic networks and is a more complicated cellular process than initially thought (Kimchi, 2007).…”

Carbohydrate utilization and the lager yeast transcriptome during brewery fermentation

“…Technology is now available to determine the genome-wide transcriptional response of yeast to environmental changes and has been used to elucidate the transcriptional response to a number of brewery-relevant parameters, including, for example, availability of oxygen and anaerobiosis (Aguilera et al, 2005;Lai et al, 2005), ageing (Fabrizio et al, 2005;Laun et al, 2005), dehydration and hydration (Singh et al, 2005), ethanol toxicity (Alexandre et al, 2001;Caba et al, 2005;Fujita et al, 2006;van Voorst et al, 2006), glucose repression and diauxic shift (DeRisi et al, 1997;Griffin et al, 2002), nutrient limitation (Causton et al, 2001;Gasch et al, 2000), osmotic stress (Gasch et al, 2000), oxidative stress (Causton et al, 2001;Gasch et al, 2000;Koerkamp et al, 2002), pH (Causton et al, 2001), salt stress (Caba et al, 2005), sugar stress (Ando et al, 2006;Erasmus et al, 2003) and temperature change (Causton et al, 2001;Gasch et al, 2000;Homma et al, 2003;Sahara et al, 2002). However, very few studies have utilized production strains of yeast or have involved incubation in brewery wort (Smart, 2007).…”