Selective BH3-mimetics targeting BCL-2, BCL-XL or MCL-1 induce severe mitochondrial perturbations.
BCL-2 proteins
BH3-mimetics
apoptosis
mitochondria
Journal
Biological chemistry
ISSN: 1437-4315
Titre abrégé: Biol Chem
Pays: Germany
ID NLM: 9700112
Informations de publication
Date de publication:
28 01 2019
28 01 2019
Historique:
received:
25
04
2018
accepted:
07
06
2018
pubmed:
21
6
2018
medline:
1
10
2019
entrez:
21
6
2018
Statut:
ppublish
Résumé
Induction of apoptosis by selective BH3-mimetics is currently investigated as a novel strategy for cancer treatment. Here, we report that selective BH3-mimetics induce apoptosis in a variety of hematological malignancies. Apoptosis is accompanied by severe mitochondrial toxicities upstream of caspase activation. Specifically, the selective BH3-mimetics ABT-199, A-1331852 and S63845, which target BCL-2, BCL-XL and MCL-1, respectively, induce comparable ultrastructural changes including mitochondrial swelling, a decrease of mitochondrial matrix density and severe loss of cristae structure. These shared effects on mitochondrial morphology indicate a similar function of these anti-apoptotic BCL-2 proteins in maintaining mitochondrial integrity and function.
Identifiants
pubmed: 29924730
doi: 10.1515/hsz-2018-0233
pii: hsz-2018-0233
doi:
Substances chimiques
BCL2 protein, human
0
BCL2L1 protein, human
0
MCL1 protein, human
0
Myeloid Cell Leukemia Sequence 1 Protein
0
Proto-Oncogene Proteins c-bcl-2
0
bcl-X Protein
0
Caspases
EC 3.4.22.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
181-185Références
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