Postmitochondrial regulation of apoptosis by bicarbonate

Zheng Dong, Jinzhao Wang, Qiu Zhong

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Ion homeostasis may play a role in the regulation of apoptosis. The current study has shown such a role for bicarbonate (HCO3-). In apoptosis triggered by ATP depletion, the proapoptotic molecule Bax translocated from the cytosol to mitochondria, followed by cytochrome c release from the organelle, caspase activation, and development of apoptotic morphology. Apoptosis was significantly ameliorated, when HCO3- was omitted from the incubation medium. The HCO3- dependence was also demonstrated for apoptosis induced by staurosporine in HeLa cells. Of significance, when HCO3- was reintroduced, apoptosis was restored. The Cl-/HCO3- exchanger inhibitor DIDS suppressed apoptosis in HCO3--containing medium, further supporting a role for intracellular HCO3- in apoptosis regulation. We subsequently examined HCO3--dependent steps in the apoptotic cascade. Translocation of Bax and cytochrome c was not suppressed by the omission of HCO3-, suggesting HCO3- regulation at postmitochondrial levels. In vitro reconstitution of caspase activation using exogenous cytochrome c and cytosolic extracts was not HCO3- dependent. HCO3- was not required for the enzymatic activity of recombinant caspases either. In conclusion, the results have provided compelling evidence for HCO3- regulation of apoptosis. Such regulation takes place at postmitochondrial levels, downstream of Bax/cytochrome c translocation.

Original languageEnglish (US)
Pages (from-to)301-312
Number of pages12
JournalExperimental Cell Research
Volume288
Issue number2
DOIs
StatePublished - Aug 15 2003

Keywords

  • ATP depletion
  • Apoptosis
  • Apoptosome
  • Bax
  • Bicarbonate
  • Cl/HCO exchanger
  • Cytochrome c
  • Staurosporine

ASJC Scopus subject areas

  • Cell Biology

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