The molecular cell death machinery in the simple cnidarian Hydra includes an expanded caspase family and pro- and anti-apoptotic Bcl-2 proteins

Lasi, Margherita; Pauly, Barbara; Schmidt, Nina; Cikala, Mihai; Stiening, Beate; Kaesbauer, Tina; Zenner, Gerhardt; Popp, Tanja; Wagner, Anita; Knapp, Rosemary; Huber, A. H.; Grunert, Michael; Söding, Johannes; David, Charles N.; Boettger, A.

doi:10.1038/cr.2010.66

Cited by 69 publications

(115 citation statements)

References 32 publications

(37 reference statements)

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“…Hence, if the caspase cascade is arrested at an early stage, the apoptotic response does not occur. Moreover, this response may be controlled by the balance between pro-and antiapoptotic molecules, such as the Bcl-2 and Bax gene families (19,24,40). The exact biochemical sequence triggering the caspase cascade in the host remains elusive; however, based on studies in metazoan models (41), we suggest that the ROS produced by the algal symbionts compromise the structural integrity of mitochondrial membrane in the host cells, thereby stimulating the release of factors initiating a caspase cascade.…”

Section: Discussionmentioning

confidence: 99%

“…Although apoptosis has previously been suggested as a possible pathway for the demise of symbiotic cnidarians (11,12,14,19), and genes related to apoptosis have been cloned from a subset of these animals (Hydra and sea anemones) (19)(20)(21)(22)(23)(24), the pathway has not been experimentally demonstrated in hermatypic corals. Some of the characteristic morphological changes during apoptosis (but not during necrosis) include cytoplasmic shrinkage, plasma membrane blebbing, chromatin condensation, and DNA degradation.…”

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confidence: 99%

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Apoptosis and the selective survival of host animals following thermal bleaching in zooxanthellate corals

Tchernov

Kvitt

Haramaty

et al. 2011

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

182

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During the past several decades, numerous reports from disparate geographical areas have documented an increased frequency of "bleaching" in reef-forming corals. The phenomenon, triggered by increased sea surface temperatures, occurs when the cnidarian hosts digest and/or expel their intracellular, photosynthetic dinoflagellate symbionts ("zooxanthellae" in the genus Symbiodinium). Although coral bleaching is often followed by the death of the animal hosts, in some cases, the animal survives and can be repopulated with viable zooxanthellae. The physiological factors determining the ability of the coral to survive bleaching events are poorly understood. In this study, we experimentally established that bleaching and death of the host animal involve a caspase-mediated apoptotic cascade induced by reactive oxygen species produced primarily by the algal symbionts. In addition, we demonstrate that, although some corals naturally suppress caspase activity and significantly reduce caspase concentration under high temperatures as a mechanism to prevent colony death from apoptosis, even sensitive corals can be prevented from dying by application of exogenous inhibitors of caspases. Our results indicate that variability in response to thermal stress in corals is determined by a four-element, combinatorial genetic matrix intrinsic to the specific symbiotic association. Based on our experimental data, we present a working model in which the phenotypic expression of this symbiont/host relationship places a selective pressure on the symbiotic association. The model predicts the survival of the host animals in which the caspase-mediated apoptotic cascade is down-regulated.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Apoptosis and the selective survival of host animals following thermal bleaching in zooxanthellate corals

Tchernov

Kvitt

Haramaty

et al. 2011

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

182

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“…The negative effects of NO on Symbiodinium physiology (Hawkins and Davy 2012) and the links between host NO synthesis and host apoptotic-like pathway activation (Hawkins et al 2013) support this hypothesis. Apoptosis is a highly conserved mechanism of programmed cell death (Kerr et al 1972) that is regulated by caspase enzymes (Lasi et al 2010). It is an important mechanism of symbiont loss during coral bleaching (Dunn et al 2004;Weis 2008;Pernice et al 2011) and is also a pathogen-removal strategy in metazoans (Carmen and Sinai 2007).…”

Section: Communicated By Biology Editor Dr Anastazia Banaszakmentioning

confidence: 99%

Differential nitric oxide synthesis and host apoptotic events correlate with bleaching susceptibility in reef corals

et al. 2014

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Coral bleaching poses a threat to coral reefs worldwide. As a consequence of the temperature-induced breakdown in coral-dinoflagellate symbiosis, bleaching can have extensive effects on reef communities. However, our understanding of bleaching at a cellular level is limited, and this is particularly true regarding differential susceptibility among coral species. Recent work suggests that bleaching may represent a host innate immune-like response to symbiont dysfunction that involves synthesis of the signalling compound nitric oxide (NO) and the induction of host apoptotic-like cell death. In this study, we examined the activity of apoptosis-regulating enzymes alongside oxidised NO accumulation (a proxy for NO synthesis) in the reef corals Acropora millepora, Montipora digitata, and Pocillopora damicornis during experimental thermal stress. P. damicornis was the most sensitive species, suffering mortality (tissue sloughing) after 5 days at 33°C but non-lethal bleaching after 9 days at 31.5°C. A. millepora bleached at 33°C but remained structurally intact, while M. digitata showed little evidence of bleaching. P. damicornis and A. millepora both exhibited evidence of temperature-induced NO synthesis and, after 5 days of heating, levels of oxidised NO in both species were fivefold higher than in controls maintained at 28.5°C. These responses preceded bleaching by a number of days and may have occurred before symbiont dysfunction (measured as chlorophyll a degradation and oxidised NO accumulation). In A. millepora, apparent NO synthesis correlated with the induction of host apoptotic-like pathways, while in P. damicornis, the upregulation of apoptotic pathways occurred later. No evidence of elevated NO production or apoptosis was observed in M. digitata at 33°C and baseline activity of apoptosis-regulating enzymes was negligible in this species. These findings provide important physiological data in the context of the responses of corals to global change and suggest that early events in the host may be important in the collapse of the coral-dinoflagellate symbiosis.

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“…Regardless, the pathway in schistosomes is more complex than that observed in nematodes, further supporting the growing evidence that nematodes (and insects) may be evolutionary outliers with a divergent Bcl-2-regulated pathway. A similar complex pathway architecture was recently proposed for Hydra (12,13), belonging to an even more ancient phylum (cnidaria) than platyhelminthes. That pathway, however, was not fully reconstituted as we have done here with schistosome Bcl-2 family members, and Bcl-w 330 ( functional experiments with proposed Bax/Bak-like proteins were performed by using cells expressing mammalian Bax/Bak proteins and, hence, could be open to interpretation.…”

Section: Discussionmentioning

confidence: 99%

“…In insects, a prosurvival protein (Buffy) and a Bax/Bak ortholog (Debcl/dBok) have been described, although the control of the pathway is dominated by proteins of the inhibitor of apoptosis (IAP) class that function by inhibiting caspases (9)(10)(11). More recently, Bcl-2 proteins in the fresh water polyp Hydra, from the phylum of cnidaria, have also been described (12,13). Cnidaria diverged from the metazoan lineage before the appearance of bilaterians, although they appear to have a more complex cell death machinery than either nematodes or insects as putative Bcl-2 prosurvival as well as putative proapoptotic Bax/Bak and BH3-only proteins were identified.…”

mentioning

confidence: 99%

Discovery and molecular characterization of a Bcl-2–regulated cell death pathway in schistosomes

Lee

Clarke

Evangelista

et al. 2011

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

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Schistosomiasis is an infectious disease caused by parasites of the phylum platyhelminthe. Here, we describe the identification and characterization of a Bcl-2-regulated apoptosis pathway in Schistosoma japonicum and S. mansoni. Genomic, biochemical, and cellbased mechanistic studies provide evidence for a tripartite pathway, similar to that in humans including BH3-only proteins that are inhibited by prosurvival Bcl-2-like molecules, and Bax/Bak-like proteins that facilitate mitochondrial outer-membrane permeabilization. Because Bcl-2 proteins have been successfully targeted with "BH3 mimetic" drugs, particularly in the treatment of cancer, we investigated whether schistosome apoptosis pathways could provide targets for future antischistosomal drug discovery efforts. Accordingly, we showed that a schistosome prosurvival protein, sjA, binds ABT-737, a well-characterized BH3 mimetic. A crystal structure of sjA bound to a BH3 peptide provides direct evidence for the feasibility of developing BH3 mimetics to target Bcl-2 prosurvival proteins in schistosomes, suggesting an alternative application for this class of drugs beyond cancer treatment.

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The molecular cell death machinery in the simple cnidarian Hydra includes an expanded caspase family and pro- and anti-apoptotic Bcl-2 proteins

Cited by 69 publications

References 32 publications

Apoptosis and the selective survival of host animals following thermal bleaching in zooxanthellate corals

Apoptosis and the selective survival of host animals following thermal bleaching in zooxanthellate corals

Differential nitric oxide synthesis and host apoptotic events correlate with bleaching susceptibility in reef corals

Discovery and molecular characterization of a Bcl-2–regulated cell death pathway in schistosomes

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