Figure 2.

Schematic depiction of multiple Nix-induced pathways for cell death in heart failure. Transcriptionally upregulated Nix localizes either to mitochondria, where it interacts with Bax and Bak to induce apoptosis via outer membrane permeabilization, or to calcium-containing sarcoplasmic reticulum (SR), where it increases calcium stores and activates the mitochondrial permeability transition pore (MPTP) independent of Bax and Bak. Mitochondrial disruption subsequent to MPTP opening leads to metabolic shutdown and death via programmed necrosis.