Postmitochondrial regulation of apoptosis by bicarbonate

Zheng Dong, Jinzhao Wang, Qiu Zhong

Research output: Contribution to journalArticle

18 Citations (Scopus)

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

Fingerprint

Bicarbonates
Apoptosis
Cytochromes c
Caspases
Chloride-Bicarbonate Antiporters
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
Staurosporine
HeLa Cells
Organelles
Cytosol
Mitochondria
Homeostasis
Adenosine Triphosphate
Ions

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Postmitochondrial regulation of apoptosis by bicarbonate. / Dong, Zheng; Wang, Jinzhao; Zhong, Qiu.

In: Experimental Cell Research, Vol. 288, No. 2, 15.08.2003, p. 301-312.

Research output: Contribution to journalArticle

Dong, Zheng ; Wang, Jinzhao ; Zhong, Qiu. / Postmitochondrial regulation of apoptosis by bicarbonate. In: Experimental Cell Research. 2003 ; Vol. 288, No. 2. pp. 301-312.
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