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The Role of the Mitochondrial Apoptosis Induced Channel MAC in Cytochrome c Release

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Abstract

Permeabilization of the mitochondrial outer membrane is a crucial event during apoptosis. It allows the release of proapoptotic factors, like cytochrome c, from the intermembrane space, and represents the commitment step in apoptosis. The mitochondrial apoptosis-induced channel, MAC, is a high-conductance channel that forms during early apoptosis and is the putative cytochrome c release channel. Unlike activation of the permeability transition pore, MAC formation occurs without loss of outer membrane integrity and depolarization. The single channel behavior and pharmacology of reconstituted MAC has been characterized with patch-clamp techniques. Furthermore, MAC’s activity is compared to that detected in mitochondria inside the cells at the time cytochrome c is released. Finally, the regulation of MAC by the Bcl-2 family proteins and insights concerning its molecular composition are also discussed.

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Abbreviations

MAC:

Mitochondrial apoptosis-induced channel

PTP:

Permeability transition pore

TOM:

Translocase of the outer membrane

VDAC:

Voltage-dependent anion-selective channel

IL-3:

Interleukin 3

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Authors and Affiliations

  1. Department of Basic Sciences, New York University, College of Dentistry, New York, New York, 10010

    Sonia Martinez-Caballero, Laurent M. Dejean & Kathleen W. Kinnally

  2. Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, 06520

    Elizabeth A. Jonas

  3. Department of Basic Sciences, New York University, College of Dentistry, 345 East 24th Street, New York, New York, 10010

    Kathleen W. Kinnally

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  1. Sonia Martinez-Caballero
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  2. Laurent M. Dejean
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  3. Elizabeth A. Jonas
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  4. Kathleen W. Kinnally
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Correspondence to Kathleen W. Kinnally.

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Martinez-Caballero, S., Dejean, L.M., Jonas, E.A. et al. The Role of the Mitochondrial Apoptosis Induced Channel MAC in Cytochrome c Release. J Bioenerg Biomembr 37, 155–164 (2005). https://doi.org/10.1007/s10863-005-6570-z

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