Functional and structural alterations in the endoplasmic reticulum and mitochondria during apoptosis triggered by C2-ceramide and CD95/APO-1/FAS receptor stimulation

Davide Ferrari, Paolo Pinton, Michelangelo Campanella, Maria Giulia Callegari, Cinzia Pizzirani, Alessandro Rimessi, Francesco Di Virgilio, Tullio Pozzan, Rosario Rizzuto

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)575-581
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume391
Issue number1
DOIs
Publication statusPublished - Jan 1 2010

Keywords

  • Apoptosis
  • Ca
  • CD95
  • Ceramide
  • Endoplasmic reticulum
  • Mitochondria

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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