Mobilization of lysosomal calcium regulates the externalization of phosphatidylserine during apoptosis.
J Biol Chem
; 284(11): 6918-23, 2009 Mar 13.
Article
em En
| MEDLINE
| ID: mdl-19126538
ABSTRACT
A hallmark of apoptotic cells is the Ca2+-dependent appearance of phosphatidylserine (PS) at the cell surface as a result of its redistribution from the inner-to-outer plasma membrane leaflet. Although endoplasmic reticulum and mitochondrial Ca2+ are known to participate in apoptosis, their role in PS externalization has not been established. In this study, several organelle-specific fluorescent markers and Ca2+-sensitive probes were used to identify the source of Ca2+ critical to PS externalization. By employing Rhod-2AM, fluorescein-labeled high molecular weight dextran, and Calcium Green 1, we provide evidence that lysosomes respond to apoptotic stimuli by releasing their luminal Ca2+ to the cytosol. Cells treated with the cytosolic phospholipase A2 inhibitor, cPLA2alpha, had no effect on caspase activation but exhibited a significant decrease in lysosomal Ca2+ release and externalization of PS in response to apoptotic stimuli. Similarly, cells depleted of lysosomal Ca2+ underwent programmed cell death yet failed to externalize PS. These data indicate that although Ca2+ release from other intracellular organelles to the cytosol is adequate for apoptosis, the release of Ca2+ from lysosomes is critical for PS externalization.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfatidilserinas
/
Cálcio
/
Apoptose
/
Citosol
/
Lisossomos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2009
Tipo de documento:
Article