Is MAC the knife that cuts cytochrome c from mitochondria during apoptosis?

L. M. Dejean; S. Martinez-Caballero; K. W. Kinnally

doi:10.1038/sj.cdd.4401949

Is MAC the knife that cuts cytochrome c from mitochondria during apoptosis?

L. M. Dejean, S. Martinez-Caballero, K. W. Kinnally

Research output: Contribution to journal › Review article › peer-review

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.

Original language	English (US)
Pages (from-to)	1387-1395
Number of pages	9
Journal	Cell Death and Differentiation
Volume	13
Issue number	8
DOIs	https://doi.org/10.1038/sj.cdd.4401949
State	Published - Aug 2006

Keywords

Apoptosis
Bax
Bcl-2
Cytochrome c
MAC
Mitochondrial apoptosis-induced channel
Patch-clamp
t-Bid

ASJC Scopus subject areas

Molecular Biology
Cell Biology

Access to Document

10.1038/sj.cdd.4401949

Cite this

@article{773918e307914837a84a31b05b2556f3,

title = "Is MAC the knife that cuts cytochrome c from mitochondria during apoptosis?",

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.",

keywords = "Apoptosis, Bax, Bcl-2, Cytochrome c, MAC, Mitochondrial apoptosis-induced channel, Patch-clamp, t-Bid",

author = "Dejean, {L. M.} and S. Martinez-Caballero and Kinnally, {K. W.}",

note = "Funding Information: 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.",

year = "2006",

month = aug,

doi = "10.1038/sj.cdd.4401949",

language = "English (US)",

volume = "13",

pages = "1387--1395",

journal = "Cell Death and Differentiation",

issn = "1350-9047",