A tale of two mitochondrial channels, MAC and PTP, in apoptosis

Kathleen W. Kinnally, Bruno Antonsson

Research output: Contribution to journalArticle

Abstract

The crucial step in the intrinsic, or mitochondrial, apoptotic pathway is permeabilization of the mitochondrial outer membrane. Permeabilization triggers release of apoptogenic factors, such as cytochrome c, from the mitochondrial intermembrane space into the cytosol where these factors ensure propagation of the apoptotic cascade and execution of cell death. However, the mechanism(s) underlying permeabilization of the outer membrane remain controversial. Two mechanisms, involving opening of two different mitochondrial channels, have been proposed to be responsible for the permeabilization; the permeability transition pore (PTP) in the inner membrane and the mitochondrial apoptosis-induced channel (MAC) in the outer membrane. Opening of PTP would lead to matrix swelling, subsequent rupture of the outer membrane, and an unspecific release of intermembrane proteins into the cytosol. However, many believe PTP opening is a consequence of apoptosis and this channel is thought to principally play a role in necrosis, not apoptosis. Activation of MAC is exquisitely regulated by Bcl-2 family proteins, which are the sentinels of apoptosis. MAC provides specific pores in the outer membrane for the passage of intermembrane proteins, in particular cytochrome c, to the cytosol. The electrophysiological characteristics of MAC are very similar to Bax channels and depletion of Bax significantly diminishes MAC activity, suggesting that Bax is an essential constituent of MAC in some systems. The characteristics of various mitochondrial channels and Bax are compared. The involvement of MAC and PTP activities in apoptosis of disease and their pharmacology are discussed.

Original languageEnglish (US)
Pages (from-to)857-868
Number of pages12
JournalApoptosis
Volume12
Issue number5
DOIs
StatePublished - May 2007

Fingerprint

Permeability
Apoptosis
Membranes
Cytosol
Mitochondrial Membranes
Cytochromes c
Proteins
Cell death
Swelling
Rupture
Cell Death
Necrosis
Chemical activation
Pharmacology

Keywords

  • Apoptosis
  • Bax
  • Bcl-2
  • MAC: Mitochondrial apoptosis-induced channel
  • Patch clamp
  • Pharmacology
  • PTP: Permeability transition pore

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

Cite this

A tale of two mitochondrial channels, MAC and PTP, in apoptosis. / Kinnally, Kathleen W.; Antonsson, Bruno.

In: Apoptosis, Vol. 12, No. 5, 05.2007, p. 857-868.

Research output: Contribution to journalArticle

Kinnally, Kathleen W. ; Antonsson, Bruno. / A tale of two mitochondrial channels, MAC and PTP, in apoptosis. In: Apoptosis. 2007 ; Vol. 12, No. 5. pp. 857-868.
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