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Apoptosis and non-inflammatory phagocytosis can be induced by mitochondrial damage without caspases.
- Source :
- Cell Death & Differentiation; May2010, Vol. 17 Issue 5, p821-832, 12p, 1 Diagram, 8 Graphs
- Publication Year :
- 2010
-
Abstract
- A central issue regarding vertebrate apoptosis is whether caspase activity is essential, particularly for its crucial biological outcome: non-inflammatory clearance of the dying cell. Caspase-9 is required for the proteolytic cascade unleashed by the mitochondrial outer membrane permeabilization (MOMP) regulated by the Bcl-2 protein family. However, despite the severely blunted apoptosis in cells from Casp9<superscript>−/−</superscript> mice, some organs with copious apoptosis, such as the thymus, appear unaffected. To address this paradox, we investigated how caspase-9 loss affects apoptosis and clearance of mouse fibroblasts and thymocytes. Although Casp9<superscript>−/−</superscript> cells were initially refractory to apoptotic insults, they eventually succumbed to slower caspase-independent cell death. Furthermore, in γ-irradiated mice, the dying Casp9<superscript>−/−</superscript> thymocytes were efficiently cleared, without apparent inflammation. Notably, MOMP proceeded normally, and the impaired mitochondrial function, revealed by diminished mitochondrial membrane potential (ΔΨ<subscript>m</subscript>), committed cells to die, as judged by loss of clonogenicity. Upon the eventual full collapse of ΔΨ<subscript>m</subscript>, presumably reflecting failure of respiration, intact dying Casp9<superscript>−/−</superscript> cells unexpectedly exposed the prototypic ‘eat-me’ signal phosphatidylserine, which allowed their recognition and engulfment by phagocytes without overt inflammation. Hence, caspase-9-induced proteolysis accelerates apoptosis, but impaired mitochondrial integrity apparently triggers a default caspase-independent program of cell death and non-inflammatory clearance. Thus, caspases appear dispensable for some essential biological functions of apoptosis. [ABSTRACT FROM AUTHOR]
- Subjects :
- CELL death
PHAGOCYTOSIS
APOPTOSIS
TUFTSIN
ANTIGEN-antibody reactions
Subjects
Details
- Language :
- English
- ISSN :
- 13509047
- Volume :
- 17
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Cell Death & Differentiation
- Publication Type :
- Academic Journal
- Accession number :
- 49128862
- Full Text :
- https://doi.org/10.1038/cdd.2009.166