Mitochondrial precursor signal peptide induces a unique permeability transition and release of cytochrome c from liver and brain mitochondria

Yulia E. Kushnareva, Brian M. Polster, Patricia M. Sokolove, Kathleen W. Kinnally, Gary Fiskum

Research output: Contribution to journalArticle

Abstract

This study tested the hypothesis that mitochondrial precursor targeting peptides can elicit the release of cytochrome c from both liver and brain mitochondria by a mechanism distinct from that mediated by the classical, Ca2+-activated permeability transition pore. Human cytochrome oxidase subunit IV signal peptide (hCOXIV1.22) at concentrations from 15 to 100 μM induced swelling, a decrease in membrane potential, and cytochrome c release in both types of mitochondria. Although cyclosporin A and bongkrekic acid were without effect, dibucaine, propanolol, dextran, and the uncoupler FCCP were each able to inhibit signal peptide-induced swelling and cytochrome c release. Adenylate kinase was coreleased with cytochrome c, arguing against a signal peptide-induced cytochrome c-specific pathway of efflux across the outer membrane. Taken together, the data indicate that a human mitochondrial signal peptide can evoke the release of cytochrome c from both liver and brain mitochondria by a unique permeability transition that differs in several characteristics from the classical mitochondrial permeability transition.

Original languageEnglish (US)
Pages (from-to)251-260
Number of pages10
JournalArchives of Biochemistry and Biophysics
Volume386
Issue number2
DOIs
StatePublished - Feb 15 2001

Fingerprint

Mitochondria
Liver Mitochondrion
Protein Sorting Signals
Cytochromes c
Liver
Permeability
Brain
Swelling
Bongkrekic Acid
Dibucaine
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
Membranes
Adenylate Kinase
Electron Transport Complex IV
Dextrans
Propranolol
Membrane Potentials
Cyclosporine
Peptides

Keywords

  • Adenylate kinase
  • Cyclosporin A
  • Dibucaine
  • Membrane potentials
  • Mitochondrial swelling
  • Propranolol

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Mitochondrial precursor signal peptide induces a unique permeability transition and release of cytochrome c from liver and brain mitochondria. / Kushnareva, Yulia E.; Polster, Brian M.; Sokolove, Patricia M.; Kinnally, Kathleen W.; Fiskum, Gary.

In: Archives of Biochemistry and Biophysics, Vol. 386, No. 2, 15.02.2001, p. 251-260.

Research output: Contribution to journalArticle

Kushnareva, Yulia E. ; Polster, Brian M. ; Sokolove, Patricia M. ; Kinnally, Kathleen W. ; Fiskum, Gary. / Mitochondrial precursor signal peptide induces a unique permeability transition and release of cytochrome c from liver and brain mitochondria. In: Archives of Biochemistry and Biophysics. 2001 ; Vol. 386, No. 2. pp. 251-260.
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