Apoptosis in yeast: triggers, pathways, subroutines

Carmona-Gutiérrez, Didac; Eisenberg, Tobias; Büttner, Sabrina; Meisinger, Chris; Kroemer, Guido; Madeo, Frank

doi:10.1038/cdd.2009.219

Cited by 438 publications

(400 citation statements)

References 90 publications

(149 reference statements)

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“…Apoptosis-like cellular suicide is also surprisingly widespread among unicellular organisms, including S. cerevisiae (29)(30)(31)37), and was present in our ancestral unicellular strain. However, apoptosis rapidly evolved a new, co-opted function in our multicellular yeast with no obvious parallel in the unicellular ancestor.…”

Section: Discussionmentioning

confidence: 99%

Experimental evolution of multicellularity

Ratcliff

Denison²,

Borrello³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

473

619

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Multicellularity was one of the most significant innovations in the history of life, but its initial evolution remains poorly understood. Using experimental evolution, we show that key steps in this transition could have occurred quickly. We subjected the unicellular yeast Saccharomyces cerevisiae to an environment in which we expected multicellularity to be adaptive. We observed the rapid evolution of clustering genotypes that display a novel multicellular life history characterized by reproduction via multicellular propagules, a juvenile phase, and determinate growth. The multicellular clusters are uniclonal, minimizing within-cluster genetic conflicts of interest. Simple among-cell division of labor rapidly evolved. Early multicellular strains were composed of physiologically similar cells, but these subsequently evolved higher rates of programmed cell death (apoptosis), an adaptation that increases propagule production. These results show that key aspects of multicellular complexity, a subject of central importance to biology, can readily evolve from unicellular eukaryotes.T he evolution of multicellularity was transformative for life on earth (1). In addition to larger size, multicellularity increased biological complexity through the formation of new biological structures. For example, multicellular organisms have evolved sophisticated, higher-level functionality via cooperation among component cells with complementary behaviors (2, 3). However, dissolution and death of multicellular individuals occurs when cooperation breaks down, cancer being a prime example (4). There are multiple mechanisms to help ensure cooperation of component cells in most extant multicellular species (5-8), but the origin and the maintenance of multicellularity are two distinct evolutionary problems. Component cells in a nascent multicellular organism would appear to have frequent opportunities to pursue noncooperative reproductive strategies at a cost to the reproduction of the multicellular individual. How, then, does the transition to multicellularity occur?Understanding the evolution of complex multicellular individuals from unicellular ancestors has been extremely challenging, largely because the first steps in this process occurred in the deep past (>200 million years ago) (9, 10). As a result, transitional forms have been lost to extinction, and little is known about the physiology, ecology, and evolutionary processes of incipient multicellularity (11). Nonetheless, several key steps have been identified for this transition. Because multicellular organisms are composed of multiple cells, the first step in this transition was likely the evolution of genotypes that form simple cellular clusters (1, 3, 12-16). It is not known whether this occurs more readily through aggregation of genetically distinct cells, as in biofilms, or by mother-daughter cell adhesion after division. Once simple clusters have evolved, selection among multicelled clusters must predominate over selection among single cells within clusters (1,15,17,18). T...

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Section: Discussionmentioning

confidence: 99%

Experimental evolution of multicellularity

Ratcliff

Denison²,

Borrello³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

473

619

View full text Add to dashboard Cite

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“…There is accumulating evidence in the baker's yeast and other eukaryotes that different stimuli induce different apoptotic pathways (42,43). In mammals, apoptosis is mediated by activation of caspases, which cleave specific substrates and trigger cell death.…”

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confidence: 99%

The Calcineurin Pathway Inhibitor Tacrolimus Enhances the In Vitro Activity of Azoles against Mucorales via Apoptosis

Shirazi

Kontoyiannis

2013

Eukaryot Cell

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The calcineurin pathway regulates antifungal drug resistance and the virulence of several major human-pathogenic fungi, including the recalcitrant Mucorales. We hypothesized that the fungistatic triazoles posaconazole (PCZ) and itraconazole (ICZ) become fungicidal in the setting of the calcineurin inhibitor tacrolimus (TCR) and that such an effect is mediated through apoptosis. Fungicidal activity and apoptosis were studied using standard microbiological techniques and hyphal metabolic and vital dye reduction assays at 37°C in RPMI 1640. Apoptosis was characterized by detecting intracellular Ca 2؉ , phosphatidylserine (PS) externalization, DNA fragmentation, plasma membrane integrity, chromatin condensation, reactive oxygen species (ROS) generation, caspase-like activity, ATP, and cytochrome c release. MICs for PCZ and ICZ alone were significantly higher (8 to 128 g/ml) than those of PCZ or ICZ plus TCR (0.25 to 4 g/ml) for Rhizopus oryzae, Cunninghamella bertholletiae, and Mucor circinelloides. Both PCZ and ICZ in combination with TCR became fungicidal, and their activity was mediated through increased apoptotic cell death of R. oryzae (10 to 50%), C. bertholletiae (5 to 50%), and M. circinelloides (5 to 55%) germlings, with morphological apoptotic changes characterized by externalization of PS, nuclear condensation, and DNA fragmentation. Moreover, activation of the caspase-like activity was correlated with cell death induced by TCR plus PCZ or ICZ. These changes correlated with elevated intracellular Ca 2؉ and ROS levels and disturbance of mitochondrial potential. We found that PCZ or ICZ in combination with TCR renders Mucorales sensitive to triazoles via apoptotic death. These observations could serve as a new paradigm for the development of new therapeutic strategies.

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“…Currently, there is increasing evidence that apoptotic-like cell death pathways exist in unicellular organisms such as yeast and that this ability confers selective advantage in adapting to adverse environmental conditions and thus ensuring survival of the clone . Therefore, it is consensual that yeast can undergo cell death with typical markers of mammalian apoptosis in response to different stimuli and possess orthologs of mammalian apoptosis regulators, supporting the existence of a primordial apoptotic machinery similar to that present in higher eukaryotic cells (for a revision see Carmona-Gutierrez et al, 2010;Pereira et al, 2008).…”

Section: A Brief Overview Of Programmed Cell Death: From Multicellulamentioning

confidence: 99%