dATP causes specific release of cytochrome c from mitochondria

Joy C. Yang, Gino A Cortopassi

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The induction of the Mitochondrial Permeability Transition (MPT) has recently been associated with the release of apoptogenic cytochrome c, which could come about in a swelling-dependent or swelling-independent manner. We observed that canonical inducers of MPT (Ca2+, t-butyl hydroperoxide, atractyloside) induce a swelling-dependent release of cytochrome c, and that osmotic support of mitochondria with PEG-1000 abolishes mitochondrial swelling, protein release, and cytochrome c release by these inducers. By contrast, it was observed that dATP is a potent inducer that caused release of cytochrome c in a swelling independent manner, i.e. even in the presence of osmotic support by PEG-1000; in addition this release of cytochrome c is inhibitable by cyclosporin A. The dATP-dependent and swelling-independent release of cytochrome c from mitochondria is not inhibitable by the protease inhibitor z-VAD, suggesting that it is not mediated by upstream caspases. This is the first report to our knowledge that a chemical compound may directly cause release of cytochrome c from mitochondria, and could explain the toxicity of dATP in the context of the genetic immunodeficiency diseases Adenosine Deaminase deficiency and Purine Nucleotide Phosphorylase deficiency.

Original languageEnglish (US)
Pages (from-to)454-457
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume250
Issue number2
DOIs
StatePublished - Sep 18 1998

Fingerprint

Mitochondria
Cytochromes c
Swelling
Permeability
Atractyloside
Mitochondrial Swelling
Purine Nucleotides
tert-Butylhydroperoxide
Phosphorylases
Inborn Genetic Diseases
Chemical compounds
Adenosine Deaminase
Mitochondrial Proteins
Caspases
Protease Inhibitors
Cyclosporine
Toxicity

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

dATP causes specific release of cytochrome c from mitochondria. / Yang, Joy C.; Cortopassi, Gino A.

In: Biochemical and Biophysical Research Communications, Vol. 250, No. 2, 18.09.1998, p. 454-457.

Research output: Contribution to journalArticle

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