C2-ceramide (C2-cer) and binding of the CD95/APO-1/FAS (aCD95) receptor are acknowledged inducers of apoptosis. In spite of that, their effects on the endoplasmic reticulum (ER) and mitochondria during early phases of apoptotic onset are poorly characterized. Here, by employing various approaches, we followed structural and functional modifications of these organelles at the beginning of cellular demise. In detail, we observed that C2-cer, but not CD95 activation, markedly modifies the morphology of the ER and promotes Ca2+ release. Accordingly, mitochondria of C2-cer-treated, but not of CD95-stimulated, cells are fragmented, show reduced Ca2+ uptake, and collapsed membrane potential (ΔΨm). Most notably, C2-cer-mediated morphological aberrations of the ER are prevented neither by the pan-caspase inhibitor Z-VADfmk nor by the cell cytoskeleton dissembler cytochalasin-D, while on the contrary they are reduced by incubation in the presence of the intracellular Ca2+ chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA). We conclude that initiation of apoptosis via the intrinsic (i.e. C2-cer mediated) pathway causes an early structural and functional alteration of both ER and mitochondria, thus underlying a final "non return" point in the apoptotic pathway.
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - Jan 1 2010|
- Endoplasmic reticulum
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology