AIF - Apoptosis Inducing Factor | Elisa - Clia - Antibody - Protein

Background:

Apoptosis-Inducing Factor (AIF) plays a significant role in apoptosis, also known as programmed cell death. AIF is primarily located in the mitochondria. It is involved in the regulation of apoptosis through both caspase-dependent and caspase-independent pathways. While most apoptotic pathways involve the activation of caspase enzymes, AIF-mediated apoptosis occurs independently of caspases. In Caspase-Independent Apoptosis, AIF-mediated apoptosis is triggered by various cellular stresses, such as DNA damage, oxidative stress, or toxins. In response to these stresses, AIF is released from the mitochondria into the cytoplasm. Once in the cytoplasm, AIF translocates to the nucleus where it induces chromatin condensation and DNA fragmentation, ultimately leading to cell death. AIF has been also implicated in several neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and Huntington's disease. Dysregulation of AIF-mediated apoptosis has been observed in the pathogenesis of these diseases, suggesting that targeting AIF could potentially be a therapeutic strategy. AIF also plays a role in maintaining mitochondrial function and integrity. It is involved in processes such as mitochondrial biogenesis and electron transport chain regulation.

Protein Structure:

• Molecular Weight: Approximately 67 kDa.
• Primary Structure: Composed of 613 amino acids.
• Domains: AIF has a mitochondrial localization signal at the N-terminus, a flavin adenine dinucleotide (FAD) binding domain, and a C-terminal apoptotic domain.
• Post-translational Modifications: AIF undergoes various modifications, including proteolytic cleavage, which is essential for its translocation from mitochondria to the nucleus during apoptosis.

Classification and Subtypes:

• Protein Family: AIF belongs to the NADH oxidase/flavin oxidoreductase family.
• Subtypes: AIF has isoforms generated through alternative splicing, such as AIF1 and AIF2, which may have different roles in cells.

Function and Biological Significance:

• Apoptosis Induction: Upon apoptotic stimuli, AIF is released from the mitochondria and translocates to the nucleus, where it induces chromatin condensation and large-scale DNA fragmentation, contributing to caspase-independent apoptosis.
• Mitochondrial Function: In its mitochondrial form, AIF is involved in maintaining mitochondrial structure and function, including oxidative phosphorylation and redox regulation.
• Cell Survival: AIF's role in cellular energy metabolism and redox homeostasis is crucial for cell survival under normal conditions.

Interactions:

• CYP450 (Cytochrome P450): AIF interacts with mitochondrial cytochrome P450, affecting electron transport and oxidative stress responses.
• PARP1 (Poly ADP-Ribose Polymerase 1): During apoptosis, PARP1 activation leads to AIF release from mitochondria.
• Endonuclease G: AIF acts in concert with endonuclease G to mediate DNA fragmentation during apoptosis.

Clinical Issues:

• Neurodegenerative Diseases: Dysregulated AIF activity and mitochondrial dysfunction have been linked to neurodegenerative diseases such as Parkinson's and Alzheimer's.
• Cancer: AIF's role in apoptosis makes it a target of interest in cancer research, where its modulation could influence tumor cell survival and death.
• Ischemia-Reperfusion Injury: AIF is implicated in cell death during ischemia-reperfusion injury, such as in heart attacks and strokes.

Summary:

Apoptosis Inducing Factor (AIF) is a critical protein involved in caspase-independent apoptosis and mitochondrial function. It plays a dual role, contributing to both cell death and survival. In the mitochondria, AIF is essential for maintaining cellular energy metabolism and redox balance, while its translocation to the nucleus triggers chromatin condensation and DNA fragmentation during apoptosis. AIF's dysregulation is associated with various diseases, including neurodegenerative disorders and cancer, making it a significant focus in biomedical research. Understanding AIF's mechanisms and interactions continues to provide insights into therapeutic strategies for these conditions.