Interfaculty Institute of Biochemistry (IFIB)

News

08.05.2017

How cells die

IFIB researchers find that calcium flux is dispensable for necroptosis

In a recent paper puplished in Cell Reports, the group of Professor Ana Garcia-Sáez at the IFIB and colleagues from the University of Zürich and the University Hospital Schleswig-Holstein show that calcium flux induced by a Smac mimetic is dispensable for necroptosis execution. The authors identify the formation of calcium-independent nanopores at the plasma membrane and find that this is important for necroptosis execution.

Necroptosis is a form of regulated necrosis that results in cell death and content release after plasma membrane permeabilization. However, little is known about the molecular events responsible for the disruption of the plasma membrane. Here, the authors find that an early increase in cytosolic calcium in TNF-induced necroptosis is mediated by treatment with a Smac mimetic via the TNF/RIP1/TAK1 survival pathway.

This does not require the activation of the necrosome and is dispensable for necroptosis. Necroptosis induced by the activation of TLR3/4 pathways does not trigger early calcium flux. It is also demonstrated that necroptotic plasma membrane rupture is mediated by osmotic forces and membrane pores around 4 nm in diameter. This late permeabilization step represents a hallmark in necroptosis execution that is cell- and treatment-independent and requires the RIP1/RIP3/MLKL core. In support of this, treatment with osmoprotectants reduces cell damage in an in vivo necroptosis model of ischemia-reperfusion injury.

Publication:

Ros U, Peña-Blanco A, Hänggi K, Kunzendorf U, Krautwald S, Wong WW, García-Sáez AJ. Necroptosis Execution Is Mediated by Plasma Membrane Nanopores Independent of Calcium. Cell Rep. 2017 Apr 4;19(1):175-187. [<link http: www.sciencedirect.com science article pii s221112471730356x external link in new>Link]

Contact:

Prof. Dr. Ana J. García Sáez

University of Tübingen

Interfaculty Institute of Biochemistry

Phone +49 7071 29 73318

<link>ana.garcia@uni-tuebingen.de

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