PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress (Articolo in rivista)

Type
Label
  • PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress (Articolo in rivista) (literal)
Anno
  • 2012-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1038/cdd.2012.74 (literal)
Alternative label
  • Verfaillie, T.; Rubio, N.; Garg, A. D.; Bultynck, G.; Rizzuto, R.; Decuypere, J-P; Piette, J.; Linehan, C.; Gupta, S.; Samali, A.; Agostinis, P. (2012)
    PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress
    in Cell death and differentiation
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Verfaillie, T.; Rubio, N.; Garg, A. D.; Bultynck, G.; Rizzuto, R.; Decuypere, J-P; Piette, J.; Linehan, C.; Gupta, S.; Samali, A.; Agostinis, P. (literal)
Pagina inizio
  • 1880 (literal)
Pagina fine
  • 1891 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://www.ncbi.nlm.nih.gov/pubmed/22705852 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 19 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 12 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 11 (literal)
Note
  • ISI Web of Science (WOS) (literal)
  • Scopu (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1, 3, 11: Laboratory of Cell Death Research and Therapy, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium; 2: Laboratory of Cell Death Research and Therapy, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium /Laboratory of Virology & Immunology, GIGA-Research B34, University of Liege, Liege, Belgium; 4, 6: Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium; 5: Department of Biomedical Sciences, Neuroscience Institute of the National Research Council (CNR), University of Padova, Padova, Italy; 7: Laboratory of Virology & Immunology, GIGA-Research B34, University of Liege, Liege, Belgium; 8, 9, 10: Apoptosis Research Centre, School of Natural Sciences, National University of Ireland, Galway, Ireland (literal)
Titolo
  • PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress (literal)
Abstract
  • Endoplasmic reticulum stress is emerging as an important modulator of different pathologies and as a mechanism contributing to cancer cell death in response to therapeutic agents. In several instances, oxidative stress and the onset of endoplasmic reticulum (ER) stress occur together; yet, the molecular events linking reactive oxygen species (ROS) to ER stress-mediated apoptosis are currently unknown. Here, we show that PERK (RNA-dependent protein kinase (PKR)-like ER kinase), a key ER stress sensor of the unfolded protein response, is uniquely enriched at the mitochondria-associated ER membranes (MAMs). PERK-/- cells display disturbed ER morphology and Ca2+ signaling as well as significantly weaker ER-mitochondria contact sites. Re-expression of a kinase-dead PERK mutant but not the cytoplasmic deletion mutant of PERK in PERK-/- cells re-establishes ER-mitochondria juxtapositions and mitochondrial sensitization to ROS-mediated stress. In contrast to the canonical ER stressor thapsigargin, during ROS-mediated ER stress, PERK contributes to apoptosis twofold by sustaining the levels of pro-apoptotic C/EBP homologous protein (CHOP) and by facilitating the propagation of ROS signals between the ER and mitochondria through its tethering function. Hence, this study reveals an unprecedented role of PERK as a MAMs component required to maintain the ER-mitochondria juxtapositions and propel ROS-mediated mitochondrial apoptosis. Furthermore, it suggests that loss of PERK may cause defects in cell death sensitivity in pathological conditions linked to ROS-mediated ER stress. Cell Death and Differentiation (2012) 19, 1880-1891; doi:10.1038/cdd.2012.74; published online 15 June 2012 (literal)
Prodotto di
Insieme di parole chiave

Incoming links:


Prodotto
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
Autore CNR di
Insieme di parole chiave di
data.CNR.it