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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

c-Jun N-terminal kinase (JNK)-mediated modulation of brain mitochondria function: new target proteins for JNK

Hagen Schroeter1, Clinton S Boyd, Ruhi Ahmed

  • 1Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles 90089-9121, USA.

The Biochemical Journal
|March 5, 2003
PubMed

Insights

c-Jun N-terminal kinase (JNK) phosphorylates mitochondrial proteins, including Bcl-2 and Bcl-x(L), triggering cytochrome c release during apoptosis. This process is independent of the mitochondrial permeability transition.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitochondrion-dependent apoptosis involves cytochrome c release.
  • Phosphorylation of Bcl-2 and Bcl-x(L) is implicated in this process.
  • The role of c-Jun N-terminal kinase (JNK) in linking protein modification to cytochrome c release requires elucidation.

Purpose of the Study:

  • To establish the interdependency between JNK signaling and mitochondrial apoptosis.
  • To investigate the mechanisms by which JNK influences mitochondrial function during apoptosis.

Main Methods:

  • Utilized isolated, bioenergetically competent rat brain mitochondria.
  • Employed two-dimensional isoelectric focusing/SDS/PAGE to detect protein phosphorylation.
  • Assessed cytochrome c release and mitochondrial inner-membrane potential (Δψm) changes.
  • Investigated the role of the inner mitochondrial membrane permeability transition (imPT) and its regulation.

Main Results:

  • JNK catalyzed the phosphorylation of Bcl-2, Bcl-x(L), and other mitochondrial proteins.
  • JNK-induced cytochrome c release occurred independently of imPT and was insensitive to cyclosporin A.
  • JNK mediated a partial collapse of Δψm, independent of imPT and cyclosporin A.
  • JNK did not induce imPT/swelling and inhibited Ca2+-induced imPT.

Conclusions:

  • JNK-dependent phosphorylation of mitochondrial proteins, including Bcl-2/Bcl-x(L), modulates mitochondrial function during apoptosis.
  • JNK signaling represents a key pathway influencing cytochrome c release and mitochondrial membrane potential.
  • The findings clarify the link between JNK, protein phosphorylation, and the apoptotic mitochondrial pathway, distinct from the classical imPT.

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