AIFM1 Human

Apoptosis-Inducing Factor, Mitochondrion-Associated, 1 (AIFM1) is a crucial protein involved in the regulation of apoptosis, a form of programmed cell death. This protein is encoded by the AIFM1 gene located on the X chromosome in humans . AIFM1 plays a significant role in both the mitochondrial respiratory chain and the induction of caspase-independent apoptosis .

AIFM1 was first described in 1999 as the first caspase-independent apoptotic inducer . It was identified as a protein that could provoke programmed cell death (PCD) after being released from the mitochondria . This discovery highlighted the central role of mitochondria in both cellular redox metabolism and the induction of PCD .

The AIFM1 protein is synthesized in the cytosol as a precursor containing 613 amino acids . It includes an N-terminal mitochondrial localization signal (MLS) that directs the protein to the mitochondrial intermembrane space (IMS) . Upon entering the IMS, the N-terminal segment is cleaved, resulting in the mature mitochondrial form of AIFM1 . This mature form anchors to the inner mitochondrial membrane and incorporates the flavin adenine dinucleotide (FAD) cofactor .

In healthy cells, AIFM1 resides in the mitochondrial intermembrane space, where it plays a vital role in redox metabolism . Upon receiving apoptotic stimuli, AIFM1 is released from the IMS into the cytosol and subsequently translocated into the nucleus . In the nucleus, AIFM1 induces chromatin condensation and large-scale DNA fragmentation, leading to cell death . This process is caspase-independent, distinguishing AIFM1 from other apoptotic factors that rely on caspase activation .

AIFM1 is a key player in the intrinsic pathway of apoptosis. It triggers chromatin condensation and DNA fragmentation, essential steps in the apoptotic process . The release of AIFM1 from the mitochondria to the cytosol and its subsequent translocation to the nucleus are critical events in the execution of apoptosis . This protein’s ability to induce apoptosis without the involvement of caspases makes it a unique and important factor in cell death regulation .

The study of AIFM1 has significant implications for understanding various diseases and conditions where apoptosis plays a crucial role. Dysregulation of apoptosis can lead to conditions such as cancer, neurodegenerative diseases, and immune disorders . Understanding the mechanisms of AIFM1 and its role in apoptosis can provide insights into potential therapeutic targets for these diseases .