title: Human initiator caspases trigger apoptotic and autophagic phenotypes in Saccharomyces cerevisiae.
abstract: Caspases are a family of proteases that participate in the progression and execution of the apoptotic program. However, regulation of the caspase activation and their substrates has not yet been fully elucidated. Here we explore the effect of the ectopic expression of the human initiator caspases-8 and -10 in Saccharomyces cerevisiae. Our results showed that the expression of human CASP10 and CASP8 triggers certain apoptotic markers such as a massive production of reactive oxygen species (ROS), chromatin condensation and phosphatidylserine externalization, finally leading to cell death. In response to hydroxyurea (HU), yeast cells expressing caspase-10 did not reduce the replication of DNA and escaped to the intra-S checkpoint of the cell cycle. In addition, caspase-10 expression induced yeast vacuolization and a vacuole-associated phenotype resembling autophagy. Other intracellular alterations such as disorganization of the actin cytoskeleton, cell wall damage, and aberrations within the endoplasmic reticulum lumen were also associated with caspase-10 expression. Furthermore, caspase-induced cell death was completely dependent on the proteolytic activation of the enzyme but, in contrast, was not dependent on either of the endogenous yeast apoptotic proteins Aif1 and Mca1 or the mitochondria.
authors.affiliation: Instituto de Microbiología Bioquímica y Departamento de Microbiología y Genética, CSIC/Universidad de Salamanca, Campus Miguel de Unamuno, E-37007 Salamanca, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lisa-Santamaría
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Neiman
authors.forename: Alvaro
authors.initials: A
authors.lastname: Cuesta-Marbán
authors.forename: Faustino
authors.initials: F
authors.lastname: Mollinedo
authors.forename: José L
authors.initials: JL
authors.lastname: Revuelta
authors.forename: Alberto
authors.initials: A
authors.lastname: Jiménez
mesh_terms: D017209:Apoptosis; D001343:Autophagy; D053455:Caspase 10 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism*; D002453:Cell Cycle; D016923:Cell Death; D006801:Humans; D019169:Jurkat Cells; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D053455:Caspase 10; D053181:Caspase 8; C506438:CASP10 protein, human