Electrophysiological study of a novel large pore formed by Bax and the voltage-dependent anion channel that is permeable to cytochrome c

Shigeomi Shimizu, Toru Ide, Toshio Yanagida, Yoshihide Tsujimoto

Research output: Contribution to journalArticle

274 Citations (Scopus)

Abstract

The Bcl-2 family of proteins, consisting of anti-apoptotic and pro- apoptotic members, regulates cell death by controlling mitochondrial membrane permeability that is crucial for apoptotic signal transduction. We have recently shown that some of these proteins, such as Bcl-x(L), Bax, and Bak, directly modulate the mitochondrial voltage-dependent anion channel (VDAC) and thus regulate apoptogenic cytochrome c release and potential loss. To elucidate the molecular mechanisms of VDAC regulation by Bcl-2 family proteins, an electrophysiological study was carried out. It was found that VDAC and pro-apoptotic Bax created a large pore, with conductance levels 4- and 10-fold greater than those of the VDAC and Bax channels, respectively. Although the VDAC and Bax channels both show ion selectivity and voltage- dependent modulation of their activity, the VDAC-Bax channel had neither of their properties. Anti-apoptotic Bcl-x(L) and its BH4 oligopeptide completely closed the VDAC, in contrast to the Bax. Cytochrome c passed through a single VDAC-Bax channel but not through the VDAC or Bax channel in a planar lipid bilayer. These data provide direct evidence that VDAC forms a novel large pore together with Bax.

Original languageEnglish
Pages (from-to)12321-12325
Number of pages5
JournalJournal of Biological Chemistry
Volume275
Issue number16
DOIs
Publication statusPublished - Apr 21 2000
Externally publishedYes

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Voltage-Dependent Anion Channels
Cytochromes c
Signal transduction
Oligopeptides
Apoptosis Regulatory Proteins
Lipid bilayers
Mitochondrial Membranes
Lipid Bilayers
Cell death
Permeability
Signal Transduction
Proteins
Cell Death

ASJC Scopus subject areas

  • Biochemistry

Cite this

Electrophysiological study of a novel large pore formed by Bax and the voltage-dependent anion channel that is permeable to cytochrome c. / Shimizu, Shigeomi; Ide, Toru; Yanagida, Toshio; Tsujimoto, Yoshihide.

In: Journal of Biological Chemistry, Vol. 275, No. 16, 21.04.2000, p. 12321-12325.

Research output: Contribution to journalArticle

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