Illuminating mitochondrial permeabilisation in apoptosis

Ana García-Sáez

Max Planck Institute of Biophysics, Membrane Dynamics, Max-von-Laue-Str. 3, 60438 Frankfurt am Main, Germany, ana.garcia@biophys.mpg.de

Mitochondrial permeabilization is a key step in the signaling pathway of apoptosis and in the cell’s commitment to death. It affects the outer and subsequently the inner mitochondrial membranes through the opening of membrane pores via mechanisms that are not fully clear. This releases cytochrome c and SMAC into the cytosol, leading to the activation of caspases, a set of proteases that accelerate cell death and that block inflammation by inactivating intracellular innate immunity effectors. Mitochondrial inner membrane permeabilization additionally releases mtDNA into the cytosol, which in turn activates intracellular innate immunity pathways unless counterbalanced by caspases. Here, I will discuss our work using advanced microscopy methods to advance our understanding of the molecular mechanisms of mitochondrial pores in apoptosis and how they function in the regulation of cell death and of inflammatory signaling outcomes.

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