Mitochondrial overproduction of ROS causes increased intracellular Ca++, which activates the calcium-activated neutral cysteine protease calpain. Calpain then activates the Ca2+/calmodulin-dependent /CaM) (Ca2+)serine/threonine phosphatase calcineurin. Dephosphorylation facilitates nuclear translocation of the transcription factor Nuclear Factor of Activated T Cells (NFAT). In the nucleus, NFAT interacts with polyADP-ribose polymerase (PARP), which increases NFAT transcriptional activity via NFAT polyADP ribosylation. MCP-1, monocyte chemoattractant protein-1; ICAM-1, Intercellular Adhesion Molecule 1; IL-6, Interleukin-6.