Hindawi Publishing CorporationOxidative Medicine and Cellular LongevityVolume 2013, Article ID 684395, 3 pageshttp://dx.doi.org/10.1155/2013/684395
EditorialYeast Stress, Aging, and Death
Cristina Mazzoni,1 Sergio Giannattasio,2 Joris Winderickx,3 and Paula Ludovico4,5
1 Pasteur Institute-Cenci Bolognetti Foundation, Department of Biology and Biotechnology Charles Darwin Sapienza,University of Rome, 00185 Rome, Italy
2 National Research Council-Institute of Biomembranes and Bioenergetics, Via Amendola 165/a, 70126 Bari, Italy3 Functional Biology, KU Leuven, Kasteelpark Arenberg 31, 3001 Heverlee, Belgium4Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, 4710-057 Braga, Portugal5 ICVS/3B’s–PT Government Associate Laboratory, Braga, Guimaraes, Portugal
Correspondence should be addressed to Cristina Mazzoni; [email protected]
Until about 15 years ago, programmed cell death (PCD),at that time mainly defined as apoptosis, was believed tobe a feature occurring only in metazoans to ensure properembryonic development, cell differentiation, and regulationof the immune response. However, the discovery that single-celled organisms, such as yeast, also undergo PCD challengedthis idea. Meanwhile, several key regulators and cell deathexecuters were shown to be highly conserved in yeast andother unicellular organisms, and it is now generally acceptedthat at least part of the molecular cell death machineryoriginated early in evolution.
Approximately 31% of the yeast genes have a mammalianhomologue, and an additional 30% of yeast genes showdomain similarity.This, combined with the ease of manipula-tion of yeast and the elegance of yeast genetics, has turned thislower eukaryote into an ideal system to study more complexphenomena that occur in metazoan cells, including stressresponses, mechanisms governing life span and cell death,and processes contributing to aging or human diseases likecancers and neurodegenerative disorders.
In this special issue, we collected both original researchand review articles, which combined give a nice overview onthe current status of the field.
Several papers relate to mitochondrial functions andmitochondrial dynamics, thereby documenting the piv-otal role of this organelle in aging processes and lifespan determination. In their review article, Y. Liu and
X. J. Chen discuss a novel form of mitochondria-inducedcell death in yeast cells tentatively referred to as degenerativecell death (DCD). Mutations in the adenine nucleotidetranslocase (Ant) cause aging-dependent DCD in yeast,which is sequentially manifested by inner membrane stress,mitochondrial DNA (mtDNA) loss, and progressive loss ofcell viability. Recent work revealed that the Ant-inducedDCD is suppressed by reduced cytosolic protein synthesis,suggesting a proteostatic crosstalk betweenmitochondria andthe cytosol, which may play an important role in cell survivalduring aging.
Maintenance of mtDNA is important for cell growth andsurvival. Oxidative damage to mtDNA causes respiratorydeficiency and human disease. In higher eukaryotes, themechanisms for maintenance and transmission of the mito-chondrial genome are still elusive. However, studies usingthe budding yeast Saccharomyces cerevisiae have generatedan abundance of data on how its mitochondrial genome ismaintained, and many nuclear-encoded proteins of diversefunctions appear to be involved. As such, mutations in TCAcycle enzyme-encoding genes lead to variable defects inmtDNA maintenance and respiratory deficiency. The mostsevere phenotype is caused by mutations in the ACO1 geneencoding aconitase, which has been shown to have a novelfunction inmediatingmtDNAmaintenance by directly bind-ing mtDNA. In this issue, Z. Liu and co-workers come withan alternative model to account for mtDNA loss due to an
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aco1Δmutation. On the basis of genetic evidence they foundthat intracellular iron-citrate complex toxicity contributes toaco1Δmutant phenotypes.
Mitochondrial morphology also changes during agingand similar changes are also observed when yeast cells switchtheirmetabolism from the use of fermentative carbon sourcesto nonfermentative ones and vice versa. I. W. Dawes andco-workers studied this in more detail, which led them to acorrelation between carbon source availability,mitochondrialdynamics, and autophagy. In particular, they show thatincreasing autophagy prevents mitochondrial fragmentationand that this relates directly to the determination of life span.
F. F. Severin and co-workers provide an overview anddiscussion on the role and delicate balance between mito-chondrial fission and fusion events as an ingenious mecha-nism for the removal of defectivemitochondria, a topic whichdirectly links to the pathophysiological role of mitochondrialdynamics.
It is well known that genotoxic stress contributes toaging. Also, changes in the organization of chromatin are ofparticular importance. In their research paper, G. Miloshevand co-workers examined the role of the linker histoneHho1 on chromatin organization and found this histoneto be essential for the maintenance of the chromatin loopstructures during chronological aging.
Significant progress has also beenmade in understandinghow metabolism impacts on aging and the determinationof life span. In an interesting study, M. Barile and co-workers investigated the potential metabolic regulation ofFAD by metabolites such as NAD, and they propose a novelrole of mitochondrial NAD redox status in regulating FADhomeostasis in yeast.
M. J. Sousa and co-workers report that ammoniumion shortens the chronological life span (CLS) of S. cere-visiae cells when they are starved for different auxotrophy-complementing amino acids (leucine, lysine, and histidine).Interestingly, this effect of ammonium is mediated throughdifferent pathways depending on the amino acid that is miss-ing. Therefore, this study provides interesting new insightson the underlying signalling network and as such gives newclues for the development of environmental interventionsthat extend CLS or for the identification of new therapeutictargets in diseases associated with hyperammonemia.
M. Vai and co-workers show that products of aceticacid and ethanol metabolism, rather than the compoundsthemselves, influence CLS. In particular, they show thatinhibition of ethanol metabolism by pyrazole prevents CLS.
J. A. Barcena and colleagues address two critical pro-cesses within the cell, that is, heme biosynthesis and thenonoxidative part of the pentose phosphate pathway (PPP).Particularly, the authors investigated the key enzymes uro-porphyrinogen decarboxylase (Hem12p) and transketolase(Tkl1p) and proposed a redox control mechanism for hemebiosynthesis thatmight be important in the context of tumourprogression.
K. F. Cooper and colleagues reveal that Mtl1, a cell wallstress sensor protein that activates the cell wall integritypathway (CWI) upon exposure to hydrogen peroxide, plays
an important role in the pathways leading to destruction ofcyclin C, which is involved in PCD.
S. Colombo and co-workers further investigated theinvolvement of the Ras proteins in PCD. They found thatRas-GFP relocalizes to mitochondria after abrogation of theglycolytic enzyme hexokinase 2. As this renders yeast cellsmore susceptible to acetic acid, their data suggest that thisenzyme confers protection against apoptosis in S. cerevisiae.
R. Schaffrath and co-workers investigated how ceramidestrigger stress responses in yeast. Besides being buildingblocks for complex sphingolipids in the plasma membrane,ceramides are known to play a crucial role in the regulation ofcell proliferation and apoptosis. Here, the authors describe anovel Sit4-dependent regulatory mechanism in the ceramidestress response.
That metabolic changes play a crucial role not only at thecellular level, but also at the level of colonies is nicely doc-umented in an elegant study by Z. Palkova and co-workers.Colonies represent a well-structured and differentiated mul-ticellular community. During aging, cells within the colonyproduce ammonia as signal for metabolic reprogrammingto support long term survival. Here, the authors reveal thataging giant colonies and rapidly developing microcoloniespass through similar developmental phases, which indicatesthat the age of colony is not crucial for colony differentiation.
Finally, three papers report how yeast can be used as amodel to study human disease or to screen for drugs anddecipher their mode of action.
V. Franssens and co-workers present an elegant reviewon the benefits of using humanized yeast models to studyfundamental aspects related to protein folding diseases. Theauthors discuss the most important findings and recentadvances that assign new roles for cell wall integrity signaling,Ca2+ homeostasis, mitophagy, and cytoskeleton-mediatedtransport processes in the pathobiology underlying Parkin-son’s disease.
The research article by K. Thevissen and colleaguesdemonstrates a role for superoxide dismutases in governingtolerance of the pathogenic yeast Candida albicans to theantifungal drug Amphotericin B.
The review article by G. Farrugia and R. Balzan illustrateshow yeast research contributes to our understanding of theproapoptotic effects and the mode of action of traditionalnovel nonsteroidal anti-inflammatory drugs such as aspirin.The authors give an overview of the various proapoptoticpathways activated by these drugs and show the remarkablesimilarity of the effects triggered in yeast and mammaliancells.
In the opinion of the editors, the contributions publishedin this special issue highlight many novel features on theinterplay between metabolism, stress responses, aging, andPCD pathways and how this determines the life span of yeastcells. Insight into the matter is not only important to betterunderstand fundamental aspects of yeast physiology, but itis also of direct relevance in the context of human health, asnicely documented in several reviews.
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Acknowledgments
We, the editors, are convinced that the different contributionsshaped this special issue into an interesting and informativedocument for the readers and explicitly want to thank allauthors for sharing their data and ideas.
