Mitochondrial DNA (mtDNA) is emerging as a major driver of mitochondrial-induced inflammation. During apoptosis, the permeabilization of the mitochondrial inner membrane (MIM) through still-unclear mechanisms leads to mtDNA release into the cytosol, triggering the inflammatory GAS/STING pathway under low caspase activity. I will discuss our findings about the role of the active form of the pore-forming protein Gasdermin E (GSDME-N), which accumulates to apoptotic mitochondria, in organelle damage before plasma membrane disruption. We visualized GSDME-N pore-like nano-assemblies in the MIM of apoptotic cells, which we bridged with the cryo-EM structureof the GSDME-N pore complex in mitochondria-like membranes. I will also discuss the functional effects of GSDME depletion in cristae swelling and MIM extrusion, as well as mtDNA release and STING activation during apoptosis.