Document Detail


Vacuole-mitochondrial cross-talk during apoptosis in yeast: a model for understanding lysosome-mitochondria-mediated apoptosis in mammals.
MedLine Citation:
PMID:  21936847     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The yeast apoptosis field emerged with the finding that key components of the apoptotic machinery are conserved in these simple eukaryotes. Thus it became possible to exploit these genetically tractable organisms to improve our understanding of the intricate mechanisms of cell death in higher eukaryotes and of severe human diseases associated with apoptosis dysfunctions. Early on, it was recognized that a mitochondria-mediated apoptotic pathway showing similarities to the mammalian intrinsic pathway was conserved in yeast. Recently, lysosomes have also emerged as central players in mammalian apoptosis. Following LMP (lysosomal membrane permeabilization), lysosomal proteases such as cathepsins B, D and L are released into the cytosol and can trigger a mitochondrial apoptotic cascade. CatD (cathepsin D) can also have anti-apoptotic effects in some cellular types and specific contexts. Nonetheless, the mechanisms underlying LMP and the specific role of cathepsins after their release into the cytosol remain poorly understood. We have recently shown that yeast vacuoles, membrane-bound acidic organelles, which share many similarities to plant vacuoles and mammalian lysosomes, are also involved in the regulation of apoptosis and that the vacuolar protease Pep4p, orthologue of the human CatD, is released from the vacuole into the cytosol in response to acetic acid. Here, we discuss how the conservation of cell-death regulation mechanisms in yeast by the lysosome-like organelle and mitochondria may provide new insights into the understanding of the complex interplay between the mitochondria and lysosome-mediated signalling routes during mammalian apoptosis.
Authors:
Maria João Sousa; Flávio Azevedo; Flávìa Azevedo; Andreia Pedras; Ana Pedras; Carolina Marques; Olga P Coutinho; Ana Preto; Hernâni Gerós; Susana R Chaves; Manuela Côrte-Real
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Biochemical Society transactions     Volume:  39     ISSN:  1470-8752     ISO Abbreviation:  Biochem. Soc. Trans.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-22     Completed Date:  2012-01-17     Revised Date:  2012-02-08    
Medline Journal Info:
Nlm Unique ID:  7506897     Medline TA:  Biochem Soc Trans     Country:  England    
Other Details:
Languages:  eng     Pagination:  1533-7     Citation Subset:  IM    
Affiliation:
CBMA, Centre of Molecular and Environmental Biology, Department of Biology, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / physiology*
Humans
Lysosomes / metabolism*
Mitochondria / metabolism*
Saccharomyces cerevisiae / cytology*,  physiology*
Saccharomyces cerevisiae Proteins / metabolism
Signal Transduction / physiology*
Vacuoles / metabolism*
Chemical
Reg. No./Substance:
0/Saccharomyces cerevisiae Proteins
Comments/Corrections
Erratum In:
Biochem Soc Trans. 2011 Dec;39(6):1901
Note: Azevedo, Flávìa [corrected to Azevedo, Flávio]; Pedras, Ana [corrected to Pedras, Andreia]

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