The permeability transition pore complex in cancer cell death

doi:doi:10.1038/sj.onc.1209609

Oncogene (2006) 25, 4744–4756. doi:10.1038/sj.onc.1209609

The permeability transition pore complex in cancer cell death

C Brenner¹ and S Grimm²

¹University of Versailles/St Quentin, CNRS UMR 8159, Versailles, France
²Imperial College London, W12 ONN, Hammersmith Campus, London, UK

Correspondence: Dr C Brenner, University of Versailles/St Quentin, CNRS FRE 2445, 45 avenue des Etats-Unis, 78035 Versailles, France. E-mail: catherinebrenner@yahoo.com

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Abstract

The permeability transition pore (PTP) is a multi-protein complex at contact sites of the inner with the outer mitochondrial membrane. Research over the past years has led to the concept that the PTP occupies a central role in cell death induction. Numerous apoptosis signals convert this protein aggregate into an unspecific pore, thus activating mitochondria for the cellular self-destruction process. Here, we describe the evidence for this and the various approaches being undertaken to elucidate its subunit composition and mode of regulation. In particular, we review data that indicate a role of specific PTP subunits for apoptosis inhibition during tumorigenesis.

Keywords:

mitochondria, apoptosis, adenine nucleotide translocator, cyclophilin D, VDAC

Abbreviations:

ADP, adenosine diphosphate; ANT, adenine nucleotide translocase; ATP, adenosine 5' triphosphate; Atr, atractyloside; BA, bongrekic acid; CK, creatine kinase; CsA, cyclosporin A; CypD, Cyclophilin D; Delta Psi _m, inner transmembrane potential; HK, hexokinase; IM, inner membrane; MEF, mouse embryonic fibroblasts; OM, outer membrane; PBR, peripheral benzodiazepine receptor; PT, permeability transition; PTP, permeability transition pore; ROS, reactive oxygen species; t-BHP, tert-butylhydroperoxide; TNF, tumor necrosis factor; VDAC, voltage-dependent anion channel