The Mitochondrial Apoptosis-induced Channel (MAC) Corresponds to a Late Apoptotic Event

We have investigated the mechanism responsible for mitochondria permeabilization occurring during cell apoptosis. We have developed an in vivo model of apoptotic rat liver. Mitochondria appeared as an homogenous population in control liver. On the contrary, mitochondria varied in size, morphology, a...

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Bibliographic Details
Published in:The Journal of biological chemistry 2004-11, Vol.279 (45), p.46542-46550
Main Authors: Guihard, Gilles, Bellot, Gregory, Moreau, Carole, Pradal, Gilbert, Ferry, Nicolas, Thomy, Raphael, Fichet, Paulette, Meflah, Khaled, Vallette, François Marie
Format: Article
Language:English
Subjects:
Animals
Anions
Apoptosis
bcl-2-Associated X Protein
Biochemistry
Biochemistry, Molecular Biology
Biophysical Phenomena
Biophysics
Caspase 3
Caspases - metabolism
Cell Membrane - metabolism
Cellular Biology
Cognitive science
Education
Electrophoresis, Polyacrylamide Gel
Electrophysiology
Human health and pathology
Humanities and Social Sciences
Immunoblotting
Intracellular Membranes - metabolism
Ion Channels - chemistry
Ion Channels - physiology
Ions
Life Sciences
Liver - metabolism
Liver - pathology
Liver - ultrastructure
Microscopy, Electron
Mitochondria - metabolism
Mitochondria - pathology
Mitochondrial Proteins - chemistry
Mitochondrial Proteins - physiology
Permeability
Proto-Oncogene Proteins c-bcl-2 - metabolism
Psychology
Rats
Subcellular Processes
Time Factors
Tissues and Organs
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Summary:We have investigated the mechanism responsible for mitochondria permeabilization occurring during cell apoptosis. We have developed an in vivo model of apoptotic rat liver. Mitochondria appeared as an homogenous population in control liver. On the contrary, mitochondria varied in size, morphology, and the matrical density in apoptotic liver. Mitochondria were purified from control and apoptotic livers. In control conditions, a single mitochondrial population was identified; whereas three populations of mitochondria were purified from apoptotic liver. Our data show that these apoptotic populations correspond to early, intermediate, and late apoptotic mitochondria, which are characterized by an increasing extent of permeabilization of their outer membrane and a gradual enrichment in oligomerized Bax protein. Remarkably, a new ionic channel was observed in apoptotic but not in control mitochondria. The biophysical and pharmacological properties of this channel are in good agreement with those reported for a previously described m itochondrial a poptosis-induced c hannel (MAC) (Pavlov, E. V., Priault, M., Pietkiewicz, D., Cheng, E. H., Antonsson, B., Manon, S., Korsmeyer, S. J., Mannella, C. A., and Kinnally, K. W. (2001) J. Cell Biol. 155, 725–731). However, MAC activity was only observed in the late apoptotic mitochondrial population. Thus, our study establishes that MAC activity is related to the overall apoptotic process but corresponds to a late event.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M405153200