Caspase cleavage of cytochrome c1 disrupts mitochondrial function and enhances cytochrome c release.
Cell Res
; 22(1): 127-41, 2012 Jan.
Article
en En
| MEDLINE
| ID: mdl-21577235
ABSTRACT
Mitochondrial catastrophe can be the cause or consequence of apoptosis and is associated with a number of pathophysiological conditions. The exact relationship between mitochondrial catastrophe and caspase activation is not completely understood. Here we addressed the underlying mechanism, explaining how activated caspase could feedback to attack mitochondria to amplify further cytochrome c (cyto.c) release. We discovered that cytochrome c1 (cyto.c1) in the bc1 complex of the mitochondrial respiration chain was a novel substrate of caspase 3 (casp.3). We found that cyto.c1 was cleaved at the site of D106, which is critical for binding with cyto.c, following apoptotic stresses or targeted expression of casp.3 into the mitochondrial intermembrane space. We demonstrated that this cleavage was closely linked with further cyto.c release and mitochondrial catastrophe. These mitochondrial events could be effectively blocked by expressing non-cleavable cyto.c1 (D106A) or by caspase inhibitor z-VAD-fmk. Our results demonstrate that the cleavage of cyto.c1 represents a critical step for the feedback amplification of cyto.c release by caspases and subsequent mitochondrial catastrophe.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Citocromos c1
/
Citocromos c
/
Caspasa 3
/
Proteolisis
/
Mitocondrias
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Res
Año:
2012
Tipo del documento:
Article
País de afiliación:
China