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dc.contributor.authorTrindade, Dário Alexandre Martins-
dc.contributor.authorCôrte-Real, Manuela-
dc.contributor.authorSousa, Maria João-
dc.contributor.authorManon, Stéphen-
dc.description.abstractCeramides are second messengers of different physiological processes. Some ceramides species can have a pro-apoptotic function involving mitochondria. Indeed, ceramides are able to form pores in artificial lipid bilayers and mitochondria. Furthermore, it has been recently demonstrated that the disassembly of these pores is stimulated by anti-apoptotic proteins of the Bcl-2 family. Ceramides signaling is generally conserved, from yeast to human. Though Saccharomyces cerevisiae only possess a homolog of a BH3-only protein, it exhibits several features similar to mammalian apoptotic programmed cell death (PCD). Ours and others reports suggest the involvement of these sphingolipids in the modulation of yeast PCD during cell ageing and in response to different death stimuli. The yeast cell death program is associated to the permeabilization of the outer mitochondrial membrane (MOMP) that can be followed by the relocalization of cytochrome c to the cytosol. We observed this relocalization process during acetic acid-induced cell death and during the death induced by the heterologous expression of human pro-apoptotic protein Bax. We have shown that the permeabilization process was dependent on the presence of the adenylic nucleotides carrier (ANC) for acetic acid-induced death and was independent from ANC for Bax-induced death. While Bax-induced permeability is likely dependent on the formation of a protein channel essentially formed of Bax itself, we still do not know on which type of mechanism acetic acid-induced permeability relies on. This study aims to precise the potential role of ceramides and ceramides-formed pores in the process of MOMP and yeast programmed cell death. For this purpose, we tested the response of several S. cerevisiae BY4741 mutants on sphingolipid metabolism to Bax- and acetic acid-induced cell death. Yeast cells lacking Isc1p (unable to generate ceramide by degradation of inositolphosphosphingolipids), exhibited a higher resistance to Bax- and, consistently with data obtained with another genetic background (W303 strain), to acetic acid-induced cell death. We will discuss whether this resistance phenotype is related with a reduction in mitochondrial dysfunction induced by these death stimuli.por
dc.description.sponsorshipD.T. is supported by a F. Calouste Gulbenkian PhD grant (nº 104495). This work was financed by FEDER through POFC–COMPETE and by national funds from FCT PEst-C/BIA/UI4050/2011, FCT project FCOMP-01-0124-FEDER-007047 and Programa Pessoa (2009-10).por
dc.titleRole of ceramides and ceramides-formed pores in the process of mitochondria permeabilization and yeast programmed cell deathpor
oaire.citationConferenceDate01 - 03 Dez. 2011por
oaire.citationConferencePlaceBraga, Portugalpor
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