Spatial and temporal changes in Bax subcellular localization during anoikis

Anthony J. Valentijn, Anthony Metcalfe, C.H. Streuli, Jane Kott, A.P. Gilmore

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)599-612
Number of pages14
JournalJournal of Cell Biology
Volume162
Issue number4
DOIs
Publication statusPublished - 18 Aug 2003

Keywords

  • anoikis
  • apoprosis
  • Bax
  • mitochondria
  • caspases

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    Valentijn, A. J., Metcalfe, A., Streuli, C. H., Kott, J., & Gilmore, A. P. (2003). Spatial and temporal changes in Bax subcellular localization during anoikis. Journal of Cell Biology, 162(4), 599-612. https://doi.org/10.1083/jcb.200302154