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

Fingerprint

Apoptosis
Mitochondria
Apoptosis Regulatory Proteins
Clamping devices
Cytochromes c
Macromolecules
Liposomes
Permeability
Proteins
Monomers

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

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

Assembly of the mitochondrial apoptosis-induced channel, MAC. / Martinez-Caballero, Sonia; Dejean, Laurent M.; Kinnally, Michael S.; Oh, Kyoung Joon; Mannella, Carmen A.; Kinnally, Kathleen W.

In: Journal of Biological Chemistry, Vol. 284, No. 18, 01.05.2009, p. 12235-12245.

Research output: Contribution to journalArticle

Martinez-Caballero, S, Dejean, LM, Kinnally, MS, Oh, KJ, Mannella, CA & Kinnally, KW 2009, 'Assembly of the mitochondrial apoptosis-induced channel, MAC', Journal of Biological Chemistry, vol. 284, no. 18, pp. 12235-12245. https://doi.org/10.1074/jbc.M806610200
Martinez-Caballero S, Dejean LM, Kinnally MS, Oh KJ, Mannella CA, Kinnally KW. Assembly of the mitochondrial apoptosis-induced channel, MAC. Journal of Biological Chemistry. 2009 May 1;284(18):12235-12245. https://doi.org/10.1074/jbc.M806610200
Martinez-Caballero, Sonia ; Dejean, Laurent M. ; Kinnally, Michael S. ; Oh, Kyoung Joon ; Mannella, Carmen A. ; Kinnally, Kathleen W. / Assembly of the mitochondrial apoptosis-induced channel, MAC. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 18. pp. 12235-12245.
@article{4e6c94b9011942ca8cdc62540db6d7da,
title = "Assembly of the mitochondrial apoptosis-induced channel, MAC",
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.",
author = "Sonia Martinez-Caballero and Dejean, {Laurent M.} and Kinnally, {Michael S.} and Oh, {Kyoung Joon} and Mannella, {Carmen A.} and Kinnally, {Kathleen W.}",
year = "2009",
month = "5",
day = "1",
doi = "10.1074/jbc.M806610200",
language = "English (US)",
volume = "284",
pages = "12235--12245",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "18",

}

TY - JOUR

T1 - Assembly of the mitochondrial apoptosis-induced channel, MAC

AU - Martinez-Caballero, Sonia

AU - Dejean, Laurent M.

AU - Kinnally, Michael S.

AU - Oh, Kyoung Joon

AU - Mannella, Carmen A.

AU - Kinnally, Kathleen W.

PY - 2009/5/1

Y1 - 2009/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=66449087483&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66449087483&partnerID=8YFLogxK

U2 - 10.1074/jbc.M806610200

DO - 10.1074/jbc.M806610200

M3 - Article

C2 - 19261612

AN - SCOPUS:66449087483

VL - 284

SP - 12235

EP - 12245

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 18

ER -