Selective BH3-mimetics targeting BCL-2, BCL-X_L or MCL-1 induce severe mitochondrial perturbations

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_L or MCL-1 induce severe mitochondrial perturbations. BIOLOGICAL CHEMISTRY, 400 (2). pp. 181-185.

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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
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:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3023939