title: Spatial and temporal changes in Bax subcellular localization during anoikis.
abstract: Bax, a member of the Bcl-2 family, translocates to mitochondria during apoptosis, where it forms oligomers which are thought to release apoptogenic factors such as cytochrome c. Using anoikis as a model system, we have examined spatial and temporal changes in Bax distribution. Bax translocates to mitochondria within 15 min of detaching cells from extracellular matrix, but mitochondrial permeabilization does not occur for a number of hours. The formation of Bax oligomers and perimitochondrial clusters occurs concomitant with caspase activation and loss of mitochondrial membrane potential, before nuclear condensation. Cells can be rescued from apoptosis if they are replated onto extracellular matrix within an hour, whereas cells detached for longer could not. The loss of ability to rescue cells from anoikis occurs after Bax translocation, but before the formation of clusters and cytochrome c release. Our data suggest that Bax regulation occurs at several levels, with formation of clusters a late event, and with critical changes determining cell fate occurring earlier.
authors.affiliation: Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, 3.35 Stopford Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Valentijn
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Metcalfe
authors.forename: Jane
authors.initials: J
authors.lastname: Kott
authors.forename: Charles H
authors.initials: CH
authors.lastname: Streuli
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Gilmore
mesh_terms: D000818:Animals; D023102:Anoikis / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology; D004848:Epithelium / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein