Unraveling the molecular principles by which ceramides commit cells to death
Authors:Shashank Dadsena1, Dina G. Hassan1 and Joost C.M. Holthuis1
1 Molecular Cell Biology Division, Department of Biology/Chemistry and Center for Cellular Nanoanalytics, Osnabrück University, 49076 Osnabrück, Germany.
Keywords:
photo-activatable lipids, voltage-dependent anion channel, mitochondrial apoptosis, tumor suppressor lipid, hexokinase, ceramide transfer protein.
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflict of interest.
Please cite this article as:
Shashank Dadsena, Dina G. Hassan and Joost C.M. Holthuis (2019). Unraveling the molecular principles by which ceramides commit cells to death. Cell Stress 3(8): 280-283. doi: 10.15698/cst2019.08.196
© 2019 Dadsena et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduc-tion in any medium, provided the original author and source are acknowledged.
Abstract:
Ceramides are central intermediates of sphingolipid metabolism that can activate a variety of tumor suppressive cellular programs, including cell cycle arrest, senescence and apoptosis. Indeed, perturbations in ceramide generation and turnover are frequently linked to cancer cell survival and resistance to chemotherapy. Consequently, the potential of ceramide-based therapeutics in the treatment of cancer has become a major focus of interest. A growing body of evidence indicates that ceramides can act directly on mitochondria to trigger apoptotic cell death. However, molecular details of the underlying mechanism are scarce. In our recent study (Dadsena S et al., 2019, Nat Commun 10:1832), we used a photoactivatable ceramide probe combined with computer simulations and functional studies to identify the voltage-dependent anion channel VDAC2 as a critical effector of ceramide-induced mitochondrial apoptosis. Collectively, our findings provide a novel molecular framework for how ceramides execute their widely acclaimed anti-neoplastic activities.