BCL(X)L and BCL2 increase the metabolic fitness of breast cancer cells.............pdf (4.48 MB)
Download file

BCL(X)L and BCL2 increase the metabolic fitness of breast cancer cells: a single-cell imaging study

Download (4.48 MB)
journal contribution
posted on 02.12.2021, 15:28 by Federico Lucantoni, Manuela Salvucci, Heiko DuessmannHeiko Duessmann, Andreas Ulrich LindnerAndreas Ulrich Lindner, Diether Lambrechts, Jochen PrehnJochen Prehn
The BCL2 family of proteins regulate apoptosis by controlling mitochondrial outer membrane permeability. However, the effects on mitochondrial structure and bioenergetics have also been reported. Here we comprehensively characterized the effects of BCL2 and BCL(X)L on cellular energetics in MCF7 breast cancer cells using time-lapse confocal single-cell imaging and mitochondrial and cytosolic FRET reporters. We found that BCL2 and BCL(X)L increase the metabolic robustness of MCF7 cells, and that this was associated with increased mitochondrial NAD(P)H and ATP levels. Experiments with the F1F0 synthase inhibitor oligomycin demonstrated that BCL2 and in particular BCL(X)L, while not affecting ATP synthase activity, more efficiently coupled the mitochondrial proton motive force with ATP production. This metabolic advantage was associated with an increased resistance to nutrient deprivation and enhanced clonogenic survival in response to metabolic stress, in the absence of profound effects on cell death. Our data suggest that a primary function of BCL(X)L and BCL2 overexpression in tumor cells is to increase their resistance to metabolic stress in the tumor microenvironment, independent of cell death signaling.

Funding

Irish Cancer Society Collaborative Cancer Research Centre BREASTPREDICT (CCRC13GAL)

Science Foundation Ireland and the Health Research Board (13/IA/1881;16/US/3301)

History

Comments

The original article is available at https://www.nature.com

Published Citation

Lucantoni F, Salvucci M, Düssmann H, Lindner AU, Lambrechts D, Prehn JHM. BCL(X)L and BCL2 increase the metabolic fitness of breast cancer cells: a single-cell imaging study. Cell Death Differ. 2021;28(5):1512-1531.

Publication Date

16 December 2020

PubMed ID

33328572

Department/Unit

  • Centre for Systems Medicine
  • Physiology and Medical Physics

Research Area

  • Cancer
  • Neurological and Psychiatric Disorders

Publisher

Springer Nature Limited

Version

  • Accepted Version (Postprint)