Separation of cytochrome c-dependent caspase activation from thiol- disulfide redox change in cells lacking mitochondrial DNA

Jiyang Cai, Douglas C. Wallace, Boris Zhivotovsky, Dean P. Jones

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Release of mitochondrial cytochrome c (cyt c) is an early and common event during apoptosis. Previous studies showed that the loss of cyt c triggered superoxide production by mitochondria and contributed to the oxidation of cellular thiol-disulfide redox state. In this study, we tested whether loss of the functional electron transport chain due to depleting mitochondrial DNA (mtDNA) would affect this redox-signaling mechanism during apoptosis. Results showed that cyt c release and caspase activation in response to staurosporine treatment were preserved in cells lacking mitochondrial DNA (ρ0 cells). However, unlike the case with ρ+ cells, in which a dramatic oxidation of intracellular glutathione (GSH) occurred after mitochondrial cyt c release, the thiol-disulfide redox state in apoptotic ρ0 cells remained largely unchanged. Thus, mitochondrial signaling of caspase activation can be separated from the bioenergetic function, and mitochondrial respiratory chain is the principal source of ROS generation in staurosporine-induced apoptosis. (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)334-342
Number of pages9
JournalFree Radical Biology and Medicine
Volume29
Issue number3-4
DOIs
StatePublished - Aug 2000
Externally publishedYes

Fingerprint

Caspases
Cytochromes c
Mitochondrial DNA
Sulfhydryl Compounds
Disulfides
Oxidation-Reduction
Chemical activation
Staurosporine
Apoptosis
Electron Transport
Oxidation
Mitochondria
Superoxides
Energy Metabolism
Glutathione

Keywords

  • Adenylate kinase
  • Apoptosis
  • Cytochrome c
  • Free radicals
  • Mitochondria
  • Redox

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Medicine(all)
  • Toxicology

Cite this

Separation of cytochrome c-dependent caspase activation from thiol- disulfide redox change in cells lacking mitochondrial DNA. / Cai, Jiyang; Wallace, Douglas C.; Zhivotovsky, Boris; Jones, Dean P.

In: Free Radical Biology and Medicine, Vol. 29, No. 3-4, 08.2000, p. 334-342.

Research output: Contribution to journalArticle

Cai, Jiyang ; Wallace, Douglas C. ; Zhivotovsky, Boris ; Jones, Dean P. / Separation of cytochrome c-dependent caspase activation from thiol- disulfide redox change in cells lacking mitochondrial DNA. In: Free Radical Biology and Medicine. 2000 ; Vol. 29, No. 3-4. pp. 334-342.
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