Programmed cell death in Saccharomyces cerevisiae is hampered by the deletion of GUP1 gene

Joana Tulha,Célia Ferreira,Fábio Faria-Oliveira,Cândida Lucas

doi:10.1186/1471-2180-12-80

Abstract

BackgroundDuring the past years, yeast has been successfully established as a model to study mechanisms of programmed cell death regulation. Saccharomyces cerevisiae commits to cell death showing typical hallmarks of metazoan apoptosis, in response to different stimuli. Gup1p, an O-acyltransferase, is required for several cellular processes that are related to apoptosis development, such as rafts integrity and stability, lipid metabolism including GPI anchor correct remodeling, proper mitochondrial and vacuole function, bud site selection and actin dynamics. Therefore, we hypothesize that apoptotic process would be affected by GUP1 deletion.ResultsIn the present work we used two known apoptosis inducing conditions, chronological aging and acetic acid, to assess several apoptotic markers in gup1∆ mutant strain. We found that this mutant presents a significantly reduced chronological lifespan as compared to Wt and it is also highly sensitive to acetic acid treatment. In addition, it presents extremely high levels of ROS. There were notorious differences on apoptotic markers between Wt and gup1∆ mutant strains, namely on the maintenance of plasma membrane integrity, on the phosphatidylserine externalization, on the depolarization of mitochondrial membrane and on the chromatin condensation. Those suggested that the mutant, under either condition, probably dies of necrosis and not from apoptosis.ConclusionsTo Gup1p has been assigned an important function on lipid rafts assembly/integrity, lipid metabolism and GPI anchor remodeling. Our results provide, for the first time, the connection of the integrity of yeast lipid rafts and apoptosis induction and/or signaling, giving new insights into the molecular mechanisms underlying this process in yeast.

Highlights

IntroductionYeast has been successfully established as a model to study mechanisms of programmed cell death regulation
During the past years, yeast has been successfully established as a model to study mechanisms of programmed cell death regulation
Gup1p, an O-acyltransferase, is required for several cellular processes that are related to apoptosis development, namely, rafts integrity and stability, lipid metabolism including GPI anchor correct remodeling, proper mitochondrial and vacuole function, and actin dynamics [30,31,33,35,37,42,53,54,55,56]

Summary

Introduction

Yeast has been successfully established as a model to study mechanisms of programmed cell death regulation. Apoptosis is the most common process of programmed cell death (PCD) in eukaryotes. It is vital for the fast elimination of useless or injured cells, and for the differential development of tissues and organs. An increasing list of homologues of apoptotic regulators in metazoans has been identified in yeast, such as Yca1p, the proposed yeast caspase [9]; Aifp, the apoptosis inducing factor [10]; EndoG, an endonuclease which regulates life and death in yeast [11]; Nma111p, a yeast HtrA-like protein [12]; Bir1p, an inhibitor-of-apoptosis protein [13] and Ybh3p, a yeast protein that interacts with Bcl-xL and harbours a functional BH3 domain [14]. The old yeasts die and release certain substances (nutrients) into the medium in order to promote survival of other aged cells, yet fitter ones [6]

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