Apoptosis inducing factor is involved in initiating a caspase-independent pathway of apoptosis (positive intrinsic regulator of apoptosis) by causing DNA fragmentation and chromatin condensation. Apoptosis inducing factor is a flavoprotein. It also acts as an NADH oxidase. Another AIF function is to regulate the permeability of the mitochondrial membrane upon apoptosis. Normally it is found behind the outer membrane of the mitochondrion and is therefore secluded from the nucleus. However, when the mitochondrion is damaged, it moves to the cytosol and to the nucleus. Inactivation of AIF leads to resistance of embryonic stem cells to death following the withdrawal of growth factors indicating that it is involved in apoptosis. Function Apoptosis Inducing Factor (AIF) is a protein that triggers chromatin condensation and DNA fragmentation in a cell in order to induce programmed cell death. The mitochondrial AIF protein was found to be a caspase-independent death effector that can allow independent nuclei to undergo apoptotic changes. The process triggering apoptosis starts when the mitochondrion releases AIF, which exits through the mitochondrial membrane, enters the cytosol, and moves to the nucleus of the cell, where it signals the cell to condense its chromosomes and fragment its DNA molecules in order to prepare for cell death. Recently, researchers have discovered that the activity of AIF depends on the type of cell, the apoptotic insult, and its DNA-binding ability. AIF also plays a significant role in the mitochondrial respiratory chain and metabolic redox reactions. Synthesis The AIF protein is located across 16 exons on the X chromosome in humans. AIF1 (the most abundant type of AIF) is translated in the cytosol and recruited to the mitochondrial membrane and intermembrane space by its N-terminal mitochondrial localization signal (MLS). Inside the mitochondrion, AIF folds into its functional configuration with the help of the cofactor flavin adenine dinucleotide (FAD). A protein called Scythe (BAT3), which is used to regulate organogenesis, can increase the AIF lifetime in the cell. As a result, decreased amounts of Scythe lead to a quicker fragmentation of AIF. The X-linked inhibitor of apoptosis (XIAP) has the power to influence the half-life of AIF along with Scythe. Together, the two do not affect the AIF attached to the inner mitochondrial membrane, however they influence the stability of AIF once it exits the mitochondrion. Role in mitochondria It was thought that if a recombinant version of AIF lacked the first N-terminal 120 amino acids of