Abstract
Apoptosis is a phenomenon fundamental to higher eukaryotes and essential to mechanisms controlling tissue homeostasis. Bcl-2 family proteins tightly control this cell death program by regulating the permeabilization of the mitochondrial outer membrane and, hence, the release of cytochrome c and other proapoptotic factors. Mitochondrial apoptosis-induced channel (MAC) is the mitochondrial apoptosis-induced channel and is responsible for cytochrome c release early in apoptosis. MAC activity is detected by patch clamping mitochondria at the time of cytochrome c release. The Bcl-2 family proteins regulate apoptosis by controlling the formation of MAC. Depending on cell type and apoptotic inducer, Bax and/or Bak are structural component(s) of MAC. Overexpression of the antiapoptotic protein Bcl-2 eliminates MAC activity. The focus of this review is a biophysical characterization of MAC activity and its regulation by Bcl-2 family proteins, and ends with some discussion of therapeutic targets.
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Abbreviations
- PTP:
-
permeability transition pore
- MAC:
-
mitochondrial apoptosis-induced channel
- IL-3:
-
interleukin-3
- VDAC:
-
voltage-dependent anion-selective channel
- ANT:
-
adenine nucleotide translocator
- TOM:
-
translocase of the outer membrane
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Acknowledgements
This research was supported by NIH Grant GM57249 and NSF Grants MCB-0235834 and INT003797 to KWK. We thank Stephen Manon (Bordeaux, France) for his insightful and lively discussions and Cynthia Hughes for her excellent technical assistance. Finally, we gratefully acknowledge the huge contribution of Stan Korsmeyer to our own research program through his many years of active support and intellectual stimulation.
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Dejean, L., Martinez-Caballero, S. & Kinnally, K. Is MAC the knife that cuts cytochrome c from mitochondria during apoptosis?. Cell Death Differ 13, 1387–1395 (2006). https://doi.org/10.1038/sj.cdd.4401949
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DOI: https://doi.org/10.1038/sj.cdd.4401949
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