Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1996 Sep 1;184(3):1155-60.
doi: 10.1084/jem.184.3.1155.

Mitochondrial permeability transition is a central coordinating event of apoptosis

P Marchetti  1 , M Castedo, S A Susin, N Zamzami, T Hirsch, A Macho, A Haeffner, F Hirsch, M Geuskens, G Kroemer
Affiliations

Mitochondrial permeability transition is a central coordinating event of apoptosis

P Marchetti et al. J Exp Med. .

Abstract

In a number of experimental systems, the early stage of the apoptotic process, i.e., the stage that precedes nuclear disintegration, is characterized by the breakdown of the inner mitochondrial transmembrane potential (delta psi m). This delta psi m disruption is mediated by the opening of permeability transition (PT) pores and appears to be critical for the apoptotic cascade, since it is directly regulated by Bcl-2 and since mitochondria induced to undergo PT in vitro become capable of inducing nuclear chromatinolysis in a cell-free system of apoptosis. Here, we addressed the question of which apoptotic events are secondary to mitochondrial PT. We tested the effect of a specific inhibitor of PT, bongkrekic acid (BA), a ligand of the mitochondrial adenine nucleotide translocator, on a prototypic model of apoptosis glucocorticoid-induced thymocyte death. In addition to abolishing the apoptotic delta psi m disruption, BA prevents a number of phenomena linked to apoptosis: depletion of nonoxidized glutathione, generation of reactive oxygen species, translocation of NF kappa B, exposure of phosphatidylserine residues on the outer plasma membrane, cytoplasmic vacuolization, chromatin condensation, and oligonucleosomal DNA fragmentation. BA is also an efficient inhibitor of p53-dependent thymocyte apoptosis induced by DNA damage. These data suggest that a number of apoptotic phenomena are secondary to PT. In addition, we present data indicating that apoptotic delta psi m disruption is secondary to transcriptional events. These data connect the PT control point to the p53- and ICE/ Ced 3-regulated control points of apoptosis and place PT upstream of nuclear and plasma membrane features of PCD.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11752-6 - PubMed
    1. Cell. 1994 Oct 21;79(2):353-64 - PubMed
    1. FEBS Lett. 1995 Jan 9;357(3):242-6 - PubMed
    1. Immunol Rev. 1994 Dec;142:343-63 - PubMed
    1. J Exp Med. 1995 May 1;181(5):1661-72 - PubMed

Publication types