MAC and Bcl-2 family proteins conspire in a deadly plot

Laurent M. Dejean, Shin Young Ryu, Sonia Martinez-Caballero, Oscar Teijido, Pablo M. Peixoto, Kathleen W. Kinnally

Research output: Contribution to journalReview article

Abstract

Apoptosis is an elemental form of programmed cell death; it is fundamental to higher eukaryotes and essential to mechanisms controlling tissue homeostasis. Apoptosis is also involved in many pathologies including cancer, neurodegenerative diseases, aging, and infarcts. This cell death program is tightly regulated by Bcl-2 family proteins by controlling the formation of the mitochondrial apoptosis-induced channel or MAC. Assembly of MAC corresponds to permeabilization of the mitochondrial outer membrane, which is the so called commitment step of apoptosis. MAC provides the pathway through the mitochondrial outer membrane for the release of cytochrome c and other pro-apoptotic factors from the intermembrane space. While overexpression of anti-apoptotic Bcl-2 eliminates MAC activity, oligomers of the pro-apoptotic members Bax and/or Bak are essential structural component(s) of MAC. Assembly of MAC from Bax or Bak was monitored in real time by directly patch-clamping mitochondria with micropipettes containing the sentinel tBid, a direct activator of Bax and Bak. Herein, a variety of high affinity inhibitors of MAC (iMAC) that may prove to be crucial tools in mechanistic studies have recently been identified. This review focuses on characterization of MAC activity, its regulation by Bcl-2 family proteins, and a discussion of how MAC can be pharmacologically turned on or off depending on the pathology to be treated.

Original languageEnglish (US)
Pages (from-to)1231-1238
Number of pages8
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1797
Issue number6-7
DOIs
StatePublished - Jun 2010

Keywords

  • Apoptosis
  • Bcl-2
  • Cytochrome c
  • MAC
  • Mitochondrial apoptosis-induced channel
  • Patch-clamp

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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  • Cite this

    Dejean, L. M., Ryu, S. Y., Martinez-Caballero, S., Teijido, O., Peixoto, P. M., & Kinnally, K. W. (2010). MAC and Bcl-2 family proteins conspire in a deadly plot. Biochimica et Biophysica Acta - Bioenergetics, 1797(6-7), 1231-1238. https://doi.org/10.1016/j.bbabio.2010.01.007