Mitochondrial membrane potential regulates matrix configuration and cytochrome c release during apoptosis.
Cell Death Differ
; 10(6): 709-17, 2003 Jun.
Article
en En
| MEDLINE
| ID: mdl-12761579
ABSTRACT
During apoptosis, the mitochondrial membrane potential (MMP) decreases, but it is not known how this relates to the apoptotic process. It was recently suggested that cytochrome c is compartmentalized in closed cristal regions and therefore, matrix remodeling is required to attain complete cytochrome c release from the mitochondria. In this work we show that, at the onset of apoptosis, changes in MMP control matrix remodeling prior to cytochrome c release. Early after growth factor withdrawal the MMP declines and the matrix condenses. Both phenomena are reversed by adding oxidizable substrates. In mitochondria isolated from healthy cells, matrix condensation can be induced by either denying oxidizable substrates or by protonophores that dissipate the membrane potential. Matrix remodeling to the condensed state results in cristal unfolding and exposes cytochrome c to the intermembrane space facilitating its release from the mitochondria during apoptosis. In contrast, when a transmembrane potential is generated due to either electron transport or a pH gradient formed by acidifying the medium, mitochondria maintain an orthodox configuration in which most cytochrome c is sequestered in the cristae and is resistant to release by agents that disrupt the mitochondrial outer membrane.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carbonil Cianuro m-Clorofenil Hidrazona
/
Apoptosis
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Citosol
/
Citocromos c
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Membranas Intracelulares
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Mitocondrias
Límite:
Animals
Idioma:
En
Revista:
Cell Death Differ
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM