Apoptosis can be activated through two pathways: intrinsic and extrinsic. When the cell is under stress, intracellular signals are released from the mitochondria, activating the intrinsic pathway. The extrinsic pathway's activation relies on ligands binding to extracellular death receptors. In the intrinsic pathway, second mitochondria-derived activator of caspases (SMACs) proteins are released into the cytosol and bind to proteins that inhibit apoptosis (IAPs), which inhibits them. Caspases can then be activated and apoptosis can proceed. Cytochrome c is also released from the mitochondria and binds to apoptotic protease activating factor 1 (APAF-1) and procaspase 9 to form the apoptosome, which subsequently activates caspase 3. The extrinsic pathway can be activated through TNF as well as Fas signaling, two pathways that activate transcription factors as well as caspases involved in the inflammatory response and apoptosis.