title: Two critical factors affecting the release of mitochondrial cytochrome C as revealed by studies using N,N'-dicyclohexylcarbodiimide as an atypical inducer of permeability transition.
abstract: N,N'-dicyclohexylcarbodiimide (DCCD) was earlier reported to have stimulatory effects on mitochondrial respiration and to induce mitochondrial swelling, when it was added to mitochondrial suspensions. These data seem to imply that DCCD caused the mitochondrial permeability transition (PT), but this possibility had never been investigated. In the present study, effects of DCCD on the mitochondrial structure and function were studied in detail. DCCD was found to induce mitochondrial PT in a cyclosporine A-insensitive manner. Electron microscopic analysis also supported the induction of the mitochondrial PT by DCCD. However, different from many other PT inducers, DCCD failed to cause massive release of mitochondrial cytochrome c. To understand the relationship between the induction of mitochondrial PT and the release of mitochondrial cytochrome c, we compared the actions of DCCD on mitochondrial structure and function with those of Ca2+, known as an ordinary PT inducer. As a result, two parameters considered to be critical for controlling the release of mitochondrial cytochrome c on the induction of PT were mitochondrial volume and the velocity of mitochondrial oxygen consumption.
authors.affiliation: Institute for Genome Research, University of Tokushima, Tokushima, 770-8503, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Satsuki
authors.initials: S
authors.lastname: Terauchi
authors.forename: Aiko
authors.initials: A
authors.lastname: Tachikawa
authors.forename: Kikuji
authors.initials: K
authors.lastname: Yamashita
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kataoka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Terada
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shinohara
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism*; D004024:Dicyclohexylcarbodiimide / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004024:Dicyclohexylcarbodiimide; D045304:Cytochromes c