Unraveling the molecular principles by which ceramides commit cells to death
Dadsena, Shashank; G.Hassan, Dina; Holthuis, Joost C M;
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.
Other data
Title | Unraveling the molecular principles by which ceramides commit cells to death | Authors | Dadsena, Shashank; G.Hassan, Dina ; Holthuis, Joost C M | Keywords | ceramide transfer protein;hexokinase;mitochondrial apoptosis;photo-activatable lipids;tumor suppressor lipid;voltage-dependent anion channel | Issue Date | 16-Jul-2019 | Journal | Cell stress | Volume | 3 | Issue | 8 | Start page | 280 | End page | 283 | ISSN | 25230204 | DOI | 10.15698/cst2019.08.196 | PubMed ID | 31440742 | Scopus ID | 2-s2.0-85077903633 |
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