Cited by 193Cell death mechanisms and regulationAutophagy in Disease and TherapyCalcium signaling and nucleotide metabolism

Lysosomal membrane permeabilization and cathepsin release is a Bax/Bak-dependent, amplifying event of apoptosis in fibroblasts and monocytes

Open access
Oberle, C, Huai, J, Reinheckel, T, Tacke, M, Rassner, M, Ekert, P G, Buellesbach, J, Borner, C·2010·Cell Death & Differentiation

Abstract

Apoptotic stimuli have been shown to trigger lysosomal membrane permeability (LMP), leading to the release of cathepsins, which activate death signaling pathways in the cytosol. However, it is unknown whether this process is an initiating or amplifying event in apoptosis. In this study, we used fibroblasts and monocytes exposed to etoposide, ultraviolet light, FasL or deprived of interleukin-3 (IL-3) to show that LMP and the cytosolic release of cathepsins B, L and D consistently depends on Bax/Bak and components of the apoptosome. Neither Bax nor Bak resided on the lysosomes, indicating that lysosomes were not directly perforated by Bax/Bak but by effectors downstream of the apoptosome. Detailed kinetic analysis of cells lacking cathepsin B or L or treated with the cysteine protease inhibitor, E64d, revealed a delay in these cells in etoposide- and IL-3 deprivation-induced caspase-3 activation and apoptosis induction but not clonogenic survival, indicating that cathepsins amplify rather than initiate apoptosis.

Integrity signals

Registry

Crossref · 10.1038/cdd.2009.214

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

The text we found for this paper looks like another document, so its claims and self-check weren’t run. The registry and citation checks still apply.

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The text we found for this paper looks like another document, so the self-check wasn’t run.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Oberle, C., Huai, J., Reinheckel, T., Tacke, M., Rassner, M., Ekert, P. G., Buellesbach, J., & Borner, C.
Affiliations
  • University of Freiburg (DE)
  • Royal Children's Hospital (AU)
Corresponding author
Borner, C
Venue
Cell Death & Differentiation
Published
2010-01-22
Volume
17
Issue
7
Pages
1167-1178
ISSN
  • 1350-9047 (ISSN-L)
  • 1476-5403
OpenAlex
W2056182070
Cited by
193
References
48
Citations by year
2026: 13 · 2025: 15 · 2024: 12 · 2023: 10 · 2022: 16 · 2021: 16 · 2020: 6 · 2019: 4 · 2018: 16 · 2017: 13 · 2016: 14 · 2015: 15 · 2014: 6 · 2013: 9 · 2012: 13
FWCI
4.82
Type
journal article
Language
en
Open access
Locations
  • Cell Death and Differentiation (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Funders
  • Yale University
  • European Commission (201279)
  • Deutsche Forschungsgemeinschaft (BO-1933, GSC‐4, (EXC 294))
  • Deutsche Krebshilfe
  • Medical Research Council
  • National Health and Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
lysosomal membrane permeabilization, Bax, Bak, apoptosome, cathepsin B, cathepsin L, cathepsin D, caspase-3 activation, etoposide, Fas ligand, ultraviolet radiation, fibroblasts, monocytes, E64d
MeSH terms
Animals, Antineoplastic Agents, Phytogenic, Cathepsins, Cell Membrane Permeability, Etoposide, Fibroblasts, Interleukin-3, Leucine, Lysosomes, Monocytes, Ultraviolet Rays, Cysteine Proteinase Inhibitors, Apoptosis, bcl-2 Homologous Antagonist-Killer Protein, bcl-2-Associated X Protein, Mice, Caspase 3, Fas Ligand Protein, Apoptosomes, Gene Knockdown Techniques

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review