Pma1, a P-type Proton ATPase, Is a Determinant of Chronological Life Span in Fission Yeast (original) (raw)

A new pma1 mutation identified in a chronologically long-lived fission yeast mutant

FEBS open bio, 2014

We isolated a chronologically long-lived mutant of Schizosaccharomyces pombe and found a new mutation in pma1 (+) that encoded for an essential P-type proton ATPase. An Asp-138 to Asn mutation resulted in reduced Pma1 activity, concomitant with an increase in the chronological lifespan of this fission yeast. This study corroborates our previous report indicating Pma1 activity is crucial for the determination of life span of fission yeast, and offers information for better understanding of the enzyme, Pma1.

The Fission Yeastphp2Mutant Displays a Lengthened Chronological Lifespan

Bioscience, Biotechnology, and Biochemistry, 2013

The Schizosaccharomyces pombe php2 þ gene encodes a subunit of the CCAAT-binding factor complex. We found that disruption of the php2 þ gene extended the chronological lifespan of the fission yeast. Moreover, the lifespan of the Áphp2 mutant was barely extended under calorie restricted (CR) conditions. Many other phenotypes of the Áphp2 mutant resembled those of wild-type cells grown under CR conditions, suggesting that the Áphp2 mutant might undergo CR. The mutant also showed low respiratory activity concomitant with decreased expression of the cyc1 þ and rip1 þ genes, both of which are involved in mitochondrial electron transport. On the basis of a chromatin immunoprecipitation assay, we determined that Php2 binds to a DNA region upstream of cyc1 þ and rip1 þ in S. pombe. Here we discuss the possible mechanisms by which the chronological lifespan of Áphp2 mutant is extended.

Chronological Aging in Saccharomyces cerevisiae

Sub-cellular biochemistry, 2012

The two paradigms to study aging in Saccharomyces cerevisiae are the chronological life spanchronological life span (CLS) and the replicative life spanreplicative life span (RLS). The chronological life span is a measure of the mean and maximum survival time of non-dividing yeast populations while the replicative life span is based on the mean and maximum number of daughter cells generated by an individual mother cell before cell division stops irreversibly. Here we review the principal discoveries associated with yeast chronological aging and how they are contributing to the understanding of the aging process and of the molecular mechanisms that may lead to healthy aging in mammals. We will focus on the mechanisms of life span regulation by the Tor/Sch9Tor/Sch9 and the Ras/adenylateRas/adenylate cyclase/PKA pathwayscyclase/PKA pathways with particular emphasis on those implicating age-dependent oxidativeoxidative stressstress and DNA damage/repairDNA damage/repair .

Live fast, die soon: cell cycle progression and lifespan in yeast cells

Microbial Cell, 2015

Our understanding of lifespan has benefited enormously from the study of a simple model, the yeast Saccharomyces cerevisiae. Although a unicellular organism, yeasts undergo many of the processes directly related with aging that to some extent are conserved in mammalian cells. Nutrient-limiting conditions have been involved in lifespan extension, especially in the case of caloric restriction, which also has a direct impact on cell cycle progression. In fact, other environmental stresses (osmotic, oxidative) that interfere with normal cell cycle progression also influence the lifespan of cells, indicating a relationship between lifespan and cell cycle control. In the present review we compile and discuss new findings related to how cell cycle progression is regulated by other nutrients. We centred this review on the analysis of phosphate, also give some attention to nitrogen, and the impact of these nutrients on lifespan.

Yeast Chronological Lifespan: Longevity Regulatory Genes and Mechanisms

Cells

S. cerevisiae plays a pivotal role as a model system in understanding the biochemistry and molecular biology of mammals including humans. A considerable portion of our knowledge on the genes and pathways involved in cellular growth, resistance to toxic agents, and death has in fact been generated using this model organism. The yeast chronological lifespan (CLS) is a paradigm to study age-dependent damage and longevity. In combination with powerful genetic screening and high throughput technologies, the CLS has allowed the identification of longevity genes and pathways but has also introduced a unicellular “test tube” model system to identify and study macromolecular and cellular damage leading to diseases. In addition, it has played an important role in studying the nutrients and dietary regimens capable of affecting stress resistance and longevity and allowing the characterization of aging regulatory networks. The parallel description of the pro-aging roles of homologs of RAS, S6 k...

Regulation of chronological aging in Schizosaccharomyces pombe by the protein kinases Pka1 and Sck2

Aging Cell, 2006

Budding yeast shows a progressive decline in viability after entering stationary phase, a phenomenon known as chronological aging. We show here that the fission yeast Schizosaccharomyces pombe also undergoes chronological aging and that the process is regulated by genes controlling two related nutrient signalling pathways. The first pathway includes the serine/threonine cAMP-activated protein kinase Pka1 and the second pathway comprises the serine/threonine kinase Sck2, a homologue of Saccharomyces cerevisiae SCH9. A double mutant for pka1 and sck2 displayed an additive effect on prolonging the fission yeast lifespan, suggesting that these genes regulate related but independent pathways. These long-lived mutants also accumulated less reactive oxygen species and had a delayed initiation of apoptosis compared with wild-type cells. We also found that strains carrying pka1 deletion but not those with sck2 deletion gained resistance to oxidative stress due to exposure to H2O2 or menadione. On the other hand, the additional increase in lifespan shown by the Δpka1Δsck2 double-mutant strain correlated with an increased resistance to both oxidative stress and heat shock. These results underscore the importance of nutrient signalling pathways and reactive oxygen species on organismal lifespan and establish S. pombe as a new model organism to study the molecular mechanisms underlying aging.

Fission Yeast and Other Yeasts as Emergent Models to Unravel Cellular Aging in Eukaryotes

Journals of Gerontology Series A-biological Sciences and Medical Sciences, 2010

In the past years, simple organisms such as yeasts and worms have contributed a great deal to aging research. Studies pioneered in Saccharomyces cerevisiae were useful to elucidate a signifi cant number of molecular mechanisms underlying cellular aging and to discover novel longevity genes. Importantly, these genes proved many times to be conserved in multicellular eukaryotes. Consequently, such discovery approaches are being extended to other yeast models, such as Schizosaccharomyces pombe , Candida albicans , Kluyveromyces lactis , and Cryptococcus neoformans . In fi ssion yeast, researchers have found links between asymmetrical cell division and nutrient signaling pathways with aging. In this review, we discuss the state of knowledge on the mechanisms controlling both replicative and chronological aging in S pombe and the other emergent yeast models.

A novel gene, ecl1+, extends the chronological lifespan in fission yeast

FEMS Yeast Research, 2008

We have identified a novel gene from Schizosaccharomyces pombe that we have named ecl1 1 (extender of the chronological lifespan). When ecl1 1 is provided on a high-copy number plasmid, it extends the viability of both the Dsty1 MAP kinase mutant and the wild-type cells after entry into the stationary phase. ecl1 1 encodes an 80-amino acid polypeptide that had not been annotated in the current database. The ecl1 1-mRNA increases transiently when the growth phase is changed from the log phase to the stationary phase. The Ecl1 protein is localized in the nucleus. Calorie restriction extends the chronological lifespan of wild-type and Decl1 cells but not ecl1 1-overproducing cells. The Dpka1 mutant shows little, if any, additional extension of viability when Ecl1 is overproduced. The ste11 1 gene that is negatively controlled by Pka1 is up regulated when Ecl1 is overproduced. From these results we propose that the effect of Ecl1 overproduction may be mainly linked to and negatively affects the Pka1-dependent pathway.

Yeast replicative life span – the mitochondrial connection

FEMS Yeast Research, 2004

Mitochondria have been associated with aging in many experimental systems through the damaging action of reactive oxygen species. There is more, however, to the connection between mitochondria and Saccharomyces cerevisiae longevity and aging. Induction of the retrograde response, a pathway signaling mitochondrial dysfunction, results in the extension of life span and postponement of the manifestations of aging, changing the metabolic and stress resistance status of the cell. A paradox associated with the retrograde response is the simultaneous triggering of extrachromosomal ribosomal DNA circle (ERC) production, because of the deleterious effect these circles have on yeast longevity. The retrograde response gene RTG2 appears to play a pivotal role in ERC production, linking metabolism and genome stability. In addition to mother cell aging, mitochondria are important in establishment of age asymmetry between mother and daughter cells. The results more generally point to the existence of a mechanism to ''filter'' damaged components from daughter cells, a form of checkpoint control. Mitochondrial integrity is affected by the PHB1 and PHB2 genes, which encode inner mitochondrial membrane chaperones called prohibitins. The Phb1/2 proteins protect the cell from imbalances in the production of mitochondrial proteins. Such imbalances appear to cause a stochastic stratification of the yeast population with the appearance of short-lived cells. Ras2p impacts this process. Maintenance of mitochondrial membrane potential and the provision of Krebs cycle intermediates for biosyntheses appear to be crucial elements in yeast longevity. In sum, it is clear that mitochondria lie at the nexus of yeast longevity and aging.