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MAC, the Mitochondrial Apoptosis-Induced Channel

Introduction

File:MACcycRelease.jpg
Release of cytochrome c through MAC[1]

MAC, the Mitochondrial Apoptosis-Induced Channel, is an early marker of the onset of apoptosis[2][3]. This ion channel is formed on the outer mitochondrial membrane in response to certain apoptotic stimuli[4]. MAC activity is detected by patch clamping mitochondria from apoptotic cells at the time of cytochrome c release[5].

Members of the Bcl-2 protein family regulate apoptosis by controlling the formation of MAC: the pro-apoptotic members Bax and/or Bak form MAC[5][1], whereas the anti-apoptotic members like Bcl-2 or Bcl-xL prevent MAC formation. Once formed, MAC mediates the release of cytochrome c to the cytosol, triggering the commitment step of the mitochondrial apoptotic cascade.

References

  1. ↑ 1.0 1.1 Laurent M. Dejean, Sonia Martinez-Caballero, Stephen Manon, Kathleen W. Kinnally (2006). “Regulation of the mitochondrial apoptosis-induced channel, MAC, by BCL-2 family proteins”. Biochim Biophys Acta. 1762 (2): 191-201.
  2. ↑ Evgeny V. Pavlov, Muriel Priault, Dawn Pietkiewicz, Emily H.-Y. Cheng, Bruno Antonsson, Stephen Manon, Stanley J. Korsmeyer, Carmen A. Mannella, and Kathleen W. Kinnally (2001). “A novel, high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast”. J. Cell Biol. 155: 725-732.
  3. ↑ Liang Guo, Dawn Pietkiewicz, Evgeny V. Pavlov, Sergey M. Grigoriev, John J. Kasianowicz, Laurent M. Dejean, Stanley J. Korsmeyer, Bruno Antonsson, and Kathleen W. Kinnally (2004). “Effects of cytochrome c on the mitochondrial apoptosis-induced channel MAC”. Am. J. Physiol. Cell. Physiol. 286: C1109-C1117.
  4. ↑ Laurent M. Dejean, Sonia Martinez-Caballero, Kathleen W. Kinnally (2006). “Is MAC the knife that cuts cytochrome c from mitochondria during apoptosis?”. Cell Death and Differentiation. 13: 1387–1395.
  5. ↑ 5.0 5.1 Laurent M. Dejean, Sonia Martinez-Caballero, Liang Guo, Cynthia Hughes, Oscar Teijido, Thomas Ducret, François Ichas, Stanley J. Korsmeyer, Bruno Antonsson, Elizabeth A. Jonas, and Kathleen W. Kinnally (2005). “Oligomeric Bax Is a Component of the Putative Cytochrome c Release Channel MAC, Mitochondrial Apoptosis-induced Channel”. Mol. Biol. Cell. 16: 2424-2432.

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