Detailing the role of bax translocation, cytochrome C release, and perinuclear clustering of the mitochondria in the killing of hela cells by TNF

Bruna Pucci, Francesca Bertani, Natalie O. Karpinich, Manuela Indelicato, Matteo A. Russo, John L. Farber, Marco Tafani

Research output: Contribution to journalArticle

Abstract

Induction of cell death in HeLa cells with TNF and cycloheximide (CHX) required an adequate ATP supply and was accompanied by decrease in intracellular pH, translocation of Bax, perinuclear clustering of the mitochondria, and cytochrome c release. The chloride channel inhibitor furosemide prevented the intracellular acidification, the translocation of Bax and the cell death. Cyclosporin A (CyA) or bongkrekic acid (BK) inhibited the induction of the MPT, the release of cytochrome c and the cell death without affecting the perinuclear clustering of the mitochondria or the translocation of Bax. Energy depletion with the ATP synthase inhibitor oligomycin or the uncoupler FCCP in the presence of 2-deoxy-glucose prevented the perinuclear clustering of the mitochondria and the cell killing. However, mitochondrial translocation of Bax was still observed. By contrast, cytochrome c was released in the oligomycin-treated cells but not in the same cells treated with FCCP. The data demonstrate that apoptosis in HeLa cells is ATP dependent and requires the translocation of Bax. The movement of Bax to the mitochondria occurs before and during the perinuclear clustering of these organelles and does not require the presence of ATP. The release of cytochrome c depends on the induction of the mitochondrial permeability transition but not ATP content.

Original languageEnglish
Pages (from-to)442-449
Number of pages8
JournalJournal of Cellular Physiology
Volume217
Issue number2
DOIs
Publication statusPublished - Nov 2008

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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