Original Paper

Cell Death and Differentiation (2006) 13, 301–310. doi:10.1038/sj.cdd.4401731; published online 29 July 2005

Mitochondrial membrane permeabilization produced by PTP, Bax and apoptosis: a 1H-NMR relaxation study

Edited by JC Martinou

D Pouliquen1, G Bellot1, G Guihard1, P Fichet1, K Meflah1 and F M Vallette1

1Inserm UMR 601, Equipe 4, Institut de Biologie, 9 Quai Moncousu, 44035 Nantes cédex, France

Correspondence: D Pouliquen, Inserm UMR 601, Equipe 4, Institut de Biologie, 9 Quai Moncousu, 44035 Nantes cédex, France. Tel: +33-2-40-08-41-96; Fax: +33-2-40-08-40-82; E-mail: daniel.pouliquen@univ-nantes.fr

Received 24 January 2005; Revised 16 May 2005; Accepted 16 June 2005; Published online 29 July 2005.

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Abstract

To analyze the involvement of structured water (bound to macromolecules) in apoptosis-induced mitochondrial outer-membrane permeability, we compared the dynamics of water protons from nuclear magnetic resonance (NMR) data in apoptotic liver mitochondria with that of control mitochondria incubated in vitro with free Ca2+ (opening of the permeability transition pore, PTP) or with Bax alpha. Our results demonstrate that water molecules in apoptotic mitochondria exhibit an accelerated translational motion of structured water common with that induced by the opening of the PTP, but limited in amplitude. On the other hand, no significant quantitative change in structured water was observed in apoptotic mitochondria, a phenomenon also observed with Bax alpha-induced permeability. We conclude that the changes observed in the different water phases differ both quantitatively and qualitatively during the opening of the PTP and the Bax alpha-induced permeability, and that the apoptotic mitochondria exhibit mixed properties between these model situations.

Keywords:

apoptosis in vivo, mitochondria, water, permeability transition, Bax alpha

Abbreviations:

HCM, heavy fraction of control mitochondria;; HAM, heavy fraction of apoptotic mitochondria;; NMR, nuclear magnetic resonance; PTP, permeability transition pore

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