Mitochondrial swelling and cytochrome c release: Sensitivity to cyclosporin A and calcium

Tomoko Kanno, Hirofumi Fujita, Shikibu Muranaka, Hiromi Yano, Toshihiko Utsumi, Tamotsu Yoshioka, Masayasu Inoue, Kozo Utsumi

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


The opening of mitochondrial membrane permeability transition (MPT) pores, which results in a cyclosporin A (CsA)-sensitive and Ca 2+-dependent dissipation of the membrane potential (delta psi) and swelling (classical MPT), has been postulated to play an important role in the release of cytochrome c (Cyt.c) and also in apoptotic cell death. Recently, it has been reported that CsA-insensitive or Ca 2+-independent MPT can be classified as non-classic MPT. Therefore, we studied the effects of apoptosis-inducing agents on mitochondrial functions with respect to their CsA-sensitivity and Ca 2+-dependency. CsA-sensitive mitochondrial swelling, depolarization, and the release of Ca 2+ and Cyt.c were induced by low concentrations of arachidonic acid, triiodothyronine (T 3), or 6-hydroxdopamine but not by valinomycin and high concentrations of the fatty acid or T 3. Fe 2+/VADP and 2,2,-azobis-(2-amidinopropane) dihydrochloride (AAPH) induced swelling of mitochondria and the release of Ca 2+ and Cyt.c were not coupled with depolarization or CsA-sensitivity while dibucaine-induced swelling occurred without depolarization, Cyt.c-release or by a CsA-sensitive mechanism. A protonophoric FCCP and SF-6847 induced depolarization and Ca 2+-release occurred in a CsA-insensitive manner and failed to stimulate the release of Cyt.c. These results indicate that ambient conditions of mitochondria can greatly influence the state of membrane stability and that Cyt.c release may occur not only via a CsA-sensitive MPT but also by way of a CsA-insensitive membrane deterioration.

Original languageEnglish
Pages (from-to)91-102
Number of pages12
JournalPhysiological chemistry and physics and medical NMR
Issue number2
Publication statusPublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Physiology
  • Spectroscopy


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