Molecular mechanisms of cell death and implication in disease
Mitochondria act as a switch-board during cell death via release of proteins from the intermembrane space to the cytosol. Mechanisms of this release are in the focus of our research. Evaluation of the reactive oxygen species (ROS) generation by mitochondria as well as investigation of the effects of endo- and exogenously produced ROS on cellular energy metabolism is in our interest.
Keeping in mind accumulating evidence concerning the role of cellular metabolism in cancer development one of our projects is focusing on targeting energy producing pathways as a promising strategy in anticancer therapy. Based on our previous results, specific attention will be given to compounds sensitizing tumor cells to treatment through inhibition of glycolysis or oxidative phosphorylation.
Molecular mechanisms of apoptotic cell death (Vetenskapsrådet)
Targeting energy producing pathways as a promising strategy in neuroblastoma therapy (Barncancerfonden)
- The Swedish National Research Foundation (Vetenskapsrådet)
- The Swedish Cancer Society (Cancerfonden)
- The Swedish Childhood Cancer Foundation
- The Cancer Society in Stockholm
- The European Commission (FP-5, FP-6 and FP-7)
Zhivotovsky, B., Orrenius, S., Brustugun, O.T., and Doskeland, S.O
Injection of cytochrome c induces apoptosis.
Nature, 1998: 391, 449-450.
Zhivotovsky, B., Samali, A., Gahm, A., and Orrenius, S
Caspases: their intracellular localization and translocation during apoptosis.
Cell Death Differ., 1999: 6, 644-651.
Ott, M., Robertson, J.D., Gogvadze, V., Zhivotovsky, B., and Orrenius, S.
Cytochrome c release from mitochondria proceeds by a two-step process.
Proc. Natl. Acad. Sci, USA, 2002: 99, 1259-1263.
Orrenius, S., Zhivotovsky, B., and Nicotera, P.
Regulation of cell death: The calcium-apoptosis link.
Nature Rev. Mol. Cell Biol. 2003: 4, 552-565.
Vakifahmetoglu, H., Olsson, M., Orrenius, S., and Zhivotovsky, B.
Functional connection between p53 and caspase-2 is essential for apoptosis induced by DNA damage.
Oncogene, 2006: 25, 5683-5692.