Assembly of the mitochondrial apoptosis-induced channel, MAC

Sonia Martinez-Caballero, Laurent M. Dejean, Michael S. Kinnally, Kyoung Joon Oh, Carmen A. Mannella, Kathleen W. Kinnally

Research output: Contribution to journalArticle

Abstract

Although Bcl-2 family proteins control intrinsic apoptosis, the mechanisms underlying this regulation are incompletely understood. Patch clamp studies of mitochondria isolated from cells deficient in one or both of the pro-apoptotic proteins Bax and Bak show that at least one of the proteins must be present for formation of the cytochrome c- translocating channel, mitochondrial apoptosis-induced channel (MAC), and that the single channel behaviors of MACs containing exclusively Bax or Bak are similar. Truncated Bid catalyzes MAC formation in isolated mitochondria containing Bax and/or Bak with a time course of minutes and does not require VDAC1 or VDAC3. Mathematical analysis of the stepwise changes in conductance associated with MAC formation is consistent with pore assembly by a barrel-stave model. Assuming the staves are two transmembrane α-helices in Bax and Bak, mature MAC pores would typically contain ∼9 monomers and have diameters of 5.5-6 nm. The mitochondrial permeability data are inconsistent with formation of lipidic pores capable of transporting megadaltonsized macromolecules as observed with recombinant Bax in liposomes.

Original languageEnglish (US)
Pages (from-to)12235-12245
Number of pages11
JournalJournal of Biological Chemistry
Volume284
Issue number18
DOIs
StatePublished - May 1 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Martinez-Caballero, S., Dejean, L. M., Kinnally, M. S., Oh, K. J., Mannella, C. A., & Kinnally, K. W. (2009). Assembly of the mitochondrial apoptosis-induced channel, MAC. Journal of Biological Chemistry, 284(18), 12235-12245. https://doi.org/10.1074/jbc.M806610200