A novel, high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast

Evgeny V. Pavlov, Muriel Priault, Dawn Pietkiewicz, Emily H.Y. Cheng, Bruno Antonsson, Stephen Manon, Stanley J. Korsmeyer, Carmen A. Mannella, Kathleen W. Kinnally

Research output: Contribution to journalArticle

Abstract

During apoptosis, proapoptotic factors are released from mitochondria by as yet undefined mechanisms. Patch-clamping of mitochondria and proteoliposomes formed from mitochondrial outer membranes of mammalian (FL5.12) cells has uncovered a novel ion channel whose activity correlates with onset of apoptosis. The pore diameter inferred from the largest conductance state of this channel is ∼4 nm, sufficient to allow diffusion of cytochrome c and even larger proteins. The activity of the channel is affected by Bcl-2 family proteins in a manner consistent with their pro- or antiapoptotic properties. Thus, the channel activity correlates with presence of proapoptotic Bax in the mitochondrial outer membrane and is absent in mitochondria from cells overexpressing antiapoptotic Bcl-2. Also, a similar channel activity is found in mitochondrial outer membranes of yeast expressing human Bax. These findings implicate this channel, named mitochondrial apoptosis-induced channel, as a candidate for the outer-membrane pore through which cytochrome c and possibly other factors exit mitochondria during apoptosis.

Original languageEnglish (US)
Pages (from-to)725-731
Number of pages7
JournalJournal of Cell Biology
Volume155
Issue number5
DOIs
StatePublished - Nov 26 2001

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Keywords

  • Apoptosis
  • Bax
  • Channels
  • Mitochondria
  • Patch-clamp

ASJC Scopus subject areas

  • Cell Biology

Cite this

Pavlov, E. V., Priault, M., Pietkiewicz, D., Cheng, E. H. Y., Antonsson, B., Manon, S., Korsmeyer, S. J., Mannella, C. A., & Kinnally, K. W. (2001). A novel, high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast. Journal of Cell Biology, 155(5), 725-731. https://doi.org/10.1083/jcb.200107057