Biology:Mitochondrial apoptosis-induced channel

From HandWiki
Release of cytochrome c through MAC[1]

The mitochondrial apoptosis-induced channel (or MAC), 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,[1][5] 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. Depletion of MAC activity is accomplished pharmacologically by specific compounds, namely Bax channel inhibitors[6] and MAC inhibitors.[7] Either by knocking down MAC's main components or by its pharmacological inhibition, the end result is prevention of cytochrome c release and apoptosis.

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. doi:10.1016/j.bbadis.2005.07.002. PMID 16055309. 
  2. ↑ Evgeny V. Pavlov; Muriel Priault; Dawn Pietkiewicz; Emily H.-Y. Cheng; Bruno Antonsson; Stephen Manon; Stanley J. Korsmeyer; Carmen A. Mannella et al. (2001). "A novel, high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast". J. Cell Biol. 155 (5): 725–732. doi:10.1083/jcb.200107057. PMID 11724814. PMC 2150879. http://www.jcb.org/cgi/content/full/155/5/725. 
  3. ↑ Liang Guo; Dawn Pietkiewicz; Evgeny V. Pavlov; Sergey M. Grigoriev; John J. Kasianowicz; Laurent M. Dejean; Stanley J. Korsmeyer; Bruno Antonsson et al. (2004). "Effects of cytochrome c on the mitochondrial apoptosis-induced channel MAC". Am. J. Physiol. Cell Physiol. 286 (5): C1109–C1117. doi:10.1152/ajpcell.00183.2003. PMID 15075210. http://ajpcell.physiology.org/cgi/content/full/286/5/C1109. 
  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 (8): 1387–1395. doi:10.1038/sj.cdd.4401949. PMID 16676005. 
  5. ↑ 5.0 5.1 Laurent M. Dejean; Sonia Martinez-Caballero; Liang Guo; Cynthia Hughes; Oscar Teijido; Thomas Ducret; François Ichas; Stanley J. Korsmeyer et al. (2005). "Oligomeric Bax Is a Component of the Putative Cytochrome c Release Channel MAC, Mitochondrial Apoptosis-induced Channel". Mol. Biol. Cell 16 (5): 2424–2432. doi:10.1091/mbc.E04-12-1111. PMID 15772159. PMC 1087246. http://www.molbiolcell.org/cgi/content/full/16/5/2424. 
  6. ↑ Claudio Hetz; Pierre-Alain Vitte; Agnes Bombrun; Tatiana K. Rostovtseva; Sylvie Montessuit; Agnes Hiver; Matthias K. Schwarz; Dennis J. Church et al. (2005). "Bax Channel Inhibitors Prevent Mitochondrion-mediated Apoptosis and Protect Neurons in a Model of Global Brain Ischemia". J. Biol. Chem. 280 (52): 42960–42970. doi:10.1074/jbc.M505843200. PMID 16219766. PMC 3531726. http://www.jbc.org/content/280/52/42960.long. 
  7. ↑ Pablo M. Peixoto; Shin-Young Ryu; Agnes Bombrun; Bruno Antonsson; Kathleen W. Kinnally (2009). "MAC inhibitors suppress mitochondrial apoptosis". Biochem. J. 423 (3): 381–7. doi:10.1042/BJ20090664. PMID 19691447. http://www.biochemj.org/bj/imps/abs/BJ20090664.htm. 



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