Mitochondria are not required for death receptor-mediated cytosolic acidification during apoptosis

Mitochondria are not required for death receptor-mediated cytosolic acidification during apoptosis In addition to cell shrinkage, membrane blebbing, DNA fragmentation and phosphatidylserine exposure, intracellular acidification represents a hallmark of apoptosis. Although the mechanisms underlying cytosolic acidification during apoptosis remained largely elusive, a pivotal role of mitochondria has been proposed. In order to investigate the involvement of mitochondria in cytosolic acidification during apoptosis, we blocked the mitochondrial death pathway by overexpression of Bcl-2 and subsequently activated the death receptor pathway by anti-CD95 or TRAIL or the mitochondrial pathway by staurosporine. We show that Bcl-2 but not caspase inhibition prevented staurosporine-induced intracellular acidification. Thus, intracellular acidification in mitochondrial apoptosis is a Bcl-2-inhibitable, but caspase-independent process. In contrast, Bcl-2 only slightly delayed, but did not prevent intracellular acidification upon triggering of death receptors. The Na+/H+ exchanger NHE1 was partially degraded during apoptosis but only to a small extent and and at a delayed time point when cytosolic acidification was almost completed. We therefore conclude that cytosolic acidification is mitochondrially controlled in response to mitochondria-dependent death stimuli, but requires additional caspase-dependent mechanisms during death receptor-mediated apoptosis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Apoptosis Springer Journals

Mitochondria are not required for death receptor-mediated cytosolic acidification during apoptosis

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Publisher
Springer Journals
Copyright
Copyright © 2006 by Springer Science+Business Media, LLC
Subject
Medicine & Public Health; Virology ; Biochemistry, general; Cell Biology; Cancer Research ; Oncology
ISSN
1360-8185
eISSN
1573-675X
D.O.I.
10.1007/s10495-006-0006-z
Publisher site
See Article on Publisher Site

Abstract

In addition to cell shrinkage, membrane blebbing, DNA fragmentation and phosphatidylserine exposure, intracellular acidification represents a hallmark of apoptosis. Although the mechanisms underlying cytosolic acidification during apoptosis remained largely elusive, a pivotal role of mitochondria has been proposed. In order to investigate the involvement of mitochondria in cytosolic acidification during apoptosis, we blocked the mitochondrial death pathway by overexpression of Bcl-2 and subsequently activated the death receptor pathway by anti-CD95 or TRAIL or the mitochondrial pathway by staurosporine. We show that Bcl-2 but not caspase inhibition prevented staurosporine-induced intracellular acidification. Thus, intracellular acidification in mitochondrial apoptosis is a Bcl-2-inhibitable, but caspase-independent process. In contrast, Bcl-2 only slightly delayed, but did not prevent intracellular acidification upon triggering of death receptors. The Na+/H+ exchanger NHE1 was partially degraded during apoptosis but only to a small extent and and at a delayed time point when cytosolic acidification was almost completed. We therefore conclude that cytosolic acidification is mitochondrially controlled in response to mitochondria-dependent death stimuli, but requires additional caspase-dependent mechanisms during death receptor-mediated apoptosis.

Journal

ApoptosisSpringer Journals

Published: Dec 29, 2006

References

  • Use of intracellular pH and annexin-V flow cytometric assays to monitor apoptosis and its suppression by bcl-2 over-expression in hybridoma cell culture
    Ishaque, A; Al-Rubeai, M
  • Apoptosis induced by IL-2 withdrawal is associated with an intracellular acidification
    Rebollo, A; Gomez, J; Martinez de Aragon, A; Lastres, P; Silva, A; Perez-Sala, D
  • BCL-2 and MCL-1 expression in Chinese hamster ovary cells inhibits intracellular acidification and apoptosis induced by staurosporine
    Reynolds, JE; Li, J; Craig, RW; Eastman, A
  • Intracellular acidification during apoptosis can occur in the absence of a nucleus
    Wolf, CM; Eastman, A
  • Inhibition of Jurkat-T-lymphocyte Na+/H+-exchanger by CD95(Fas/Apo-1)-receptor stimulation
    Lang, F; Madlung, J; Bock, J; Lukewille, U; Kaltenbach, S; Lang, KS; Belka, C; Wagner, CA; Lang, HJ; Gulbins, E; Lepple-Wienhues, A
  • Renal tubular epithelial cell apoptosis is associated with caspase cleavage of the NHE1 Na+/H+ exchanger
    Wu, KL; Khan, S; Lakhe-Reddy, S; Wang, L; Jarad, G; Miller, RT; Konieczkowski, M; Brown, AM; Sedor JR; Schelling JR
  • Two CD95 (APO-1/Fas) signaling pathways
    Scaffidi, C; Fulda, S; Srinivasan, A; Friesen, C; Li, F; Tomaselli, KJ; Debatin, KM; Krammer, PH; Peter, ME

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