Journal article

Apoptosis and non-inflammatory phagocytosis can be induced by mitochondrial damage without caspases

MF van Delft, DP Smith, MH Lahoud, DCS Huang, JM Adams

CELL DEATH AND DIFFERENTIATION | NATURE PUBLISHING GROUP | Published : 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(-/-) 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(-/-) cells were initially refractory to apoptotic insults, ..

View full abstract

University of Melbourne Researchers

Grants

Awarded by National Health and Medical Research Council (NHMRC)


Awarded by NIH


Awarded by Leukemia and Lymphoma Society


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

We thank Professor A Strasser for discussions and valuable comments on the paper; V Marsden, L O'Reilly, S Jones and B Sheikh for reagents and advice; and G Siciliano, D Cooper, K Pioch and K Vella for animal care. DNA constructs encoding the soluble SIRP alpha ectodomain were kindly donated by Associate Professor Mark Wright (Monash University, Melbourne, Australia). This work was supported by a Melbourne University International Research Scholarship and Cancer Council Victoria Postdoctoral Research Fellowship to MvD, National Health and Medical Research Council (NHMRC) Fellowships to DCSH and JMA, and grants from the NHMRC (Program Grant 461221), the NIH (CA43540) and the Leukemia and Lymphoma Society (SCOR Grant 7413). Infrastructure support from NHMRC IRIISS Grant 361646 and the Victorian State Government OIS grant is gratefully acknowledged.