Henz, Kristina, Al-Zebeeby, Aoula, Basoglu, Marion, Fulda, Simone, Cohen, Gerald M, Varadarajan, Shankar ORCID: 0000-0002-8827-6567 and Vogler, Meike
(2019)
Selective BH3-mimetics targeting BCL-2, BCL-X<sub>L</sub> or MCL-1 induce severe mitochondrial perturbations.
BIOLOGICAL CHEMISTRY, 400 (2).
pp. 181-185.
Text
Henz et al Biological Chemistry 2018.pdf - Published version Download (5MB) |
Abstract
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.
Item Type: | Article |
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Uncontrolled Keywords: | apoptosis, BCL-2 proteins, BH3-mimetics, mitochondria |
Depositing User: | Symplectic Admin |
Date Deposited: | 23 Jul 2018 14:54 |
Last Modified: | 05 Oct 2023 19:54 |
DOI: | 10.1515/hsz-2018-0233 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3023939 |