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Acetic acid triggers cytochrome c release in yeast heterologously expressing hu...

Guedes, Joana P.; Baptista, Vitória; Cátia S. Pereira; Sousa, Maria João; Manon, Stéphen; Chaves, Susana R.; Côrte-Real, Manuela

Proteins of the Bcl-2 protein family, including pro-apoptotic Bax and anti-apoptotic Bcl-xL, are critical for mitochondrial-mediated apoptosis regulation. Since yeast lacks obvious orthologs of Bcl-2 family members, heterologous expression of these proteins has been used to investigate their molecular and functional aspects. Active Bax is involved in the formation of mitochondrial outer membrane pores, through ...


Lactoferrin perturbs lipid rafts and requires integrity of Pma1p-lipid rafts as...

Pereira, Cátia Sofia Santos; Andrés, María T.; Chaves, Susana Alexandra Rodrigues; Fierro, José F.; Gerós, H.; Manon, Stéphen; Rodrigues, L. R.

Lactoferrin (Lf) is a bioactive milk-derived protein with remarkable wide-spectrum antifungal activity. To deepen our understanding of the molecular mechanisms underlying Lf cytotoxicity, the role of plasma membrane ergosterol- and sphingolipid-rich lipid rafts and their association with the proton pump Pma1p was explored. Pma1p was previously identified as a Lf-binding protein. Results showed that bovine Lf (b...


Guidelines and recommendations on yeast cell death nomenclature

Carmona-Gutierrez, Didac; Bauer, Maria Anna; Zimmermann, Andreas; Aguilera, Andrés; Austriaco, Nicanor; Ayscough, Kathryn; Balzan, Rena

Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cel-lular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the defi-nition of accide...


Regulation of Bax/mitochondria interaction by AKT

Simonyan, Lilit; Renault, Thibaud T.; Novais, Maria João da Costa; Sousa, Maria João; Côrte-Real, Manuela; Camougrand, Nadine; Gonzalez, Cécile

Bax-dependent mitochondrial permeabilization during apoptosis is controlled by multiple factors, including the phosphorylation by the protein kinase AKT. We used the heterologous co-expression of human Bax and AKT1 in yeast to investigate how the kinase modulates the different steps underlying Bax activation. We found that AKT activated Bax and increased its cellular content. Both effects were dependent on Ser1...


What yeast can tell us about how cells commit suicide?

Chaves, S. R.; Coutinho, Clara Pereira; Marques, Carolina; Rodrigues, Andreia; Salin, Bénédict; Alves, Sara Cristina Sequeira; Silva, Rui; Gerós, H.

Multicellular organisms developed a complex system to balance cell proliferation and cell death in order to guarantee correct embryonic development and tissue homeostasis. Failure of cells to undergo programmed cell death (PCD) can potentially lead to severe diseases, including neural degeneration, autoimmunity and cancer. Identifying the molecules involved in PCD and understanding the regulation of the process...


Role of ceramides and ceramides-formed pores in the process of mitochondria per...

Trindade, Dário Alexandre Martins; Côrte-Real, Manuela; Sousa, Maria João; Manon, Stéphen

Ceramides 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 general...


Assessment of oxidative modification of the Aac2p carrier and its contribution ...

Trindade, Dário Alexandre Martins; Manon, Stéphen; Côrte-Real, Manuela; Sousa, Maria João


Modulation of bax mitochondrial insertion and induced cell death in yeast by ma...

Silva, Rui D.; Manon, Stéphen; Gonçalves, Jorge; Saraiva, Lucília; Côrte-Real, Manuela

Protein kinase Cα (PKCα) is a classical PKC isoform whose involvement in cell death is not completely understood. Bax, a major member of the Bcl-2 family, is required for apoptotic cell death and regulation of Bax translocation and insertion into the outer mitochondrial membrane is crucial for regulation of the apoptotic process. Here we show that PKCα increases the translocation and insertion of Bax c-myc (an ...


The importance of humanized yeast to better understand the role of Bcl-2 family...

Silva, Rui D.; Manon, Stéphen; Gonçalves, Jorge; Saraiva, Lucília; Côrte-Real, Manuela

The Bcl-2 protein family plays a central role in mitochondrial membrane permeabilization. This event and the ensuing release of cytochrome c are decisive in the apoptotic cascade. Therefore, a better knowledge of these processes and their regulation will probably lead to the development of novel therapeutic strategies for treatment of apoptosis-related diseases. However, the mode of action of Bcl-2 protein fami...


Vacuole-mitochondrial crosstalk during apoptosis induced by acetic acid in yeast

Chaves, S. R.; Coutinho, Clara Pereira; Marques, Carolina; Rodrigues, Andreia; Salin, Bénédict; Alves, Sara Cristina Sequeira; Silva, Rui; Gerós, H.


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