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A protein involved in programmed cell death

Apoptosis-inducing factor (AIF) is a protein that plays a crucial role in the process of apoptosis, or programmed cell death. It is a flavoprotein that is primarily located in the mitochondria and is involved in the regulation of cell death and cell survival.

Structure and Function

AIF is a mitochondrial intermembrane flavoprotein that, upon apoptotic stimuli, translocates to the cytosol and nucleus. In the nucleus, AIF induces chromatin condensation and large-scale DNA fragmentation, which are hallmarks of apoptosis. Unlike other apoptotic factors, AIF can induce apoptosis in a caspase-independent manner, meaning it does not require the activation of caspases, which are typically involved in the apoptotic process.

The protein is encoded by the AIFM1 gene in humans and is highly conserved across different species, indicating its essential role in cellular processes. AIF is also involved in oxidative phosphorylation and the maintenance of mitochondrial DNA.

Mechanism of Action

Upon receiving apoptotic signals, AIF is released from the mitochondria into the cytosol. This release is often triggered by the permeabilization of the outer mitochondrial membrane, a process regulated by members of the Bcl-2 family of proteins. Once in the cytosol, AIF translocates to the nucleus, where it binds to DNA and induces chromatin condensation and DNA fragmentation.

AIF's ability to induce apoptosis without caspase activation makes it a unique player in the apoptotic pathway. This caspase-independent pathway is particularly important in cells where caspase activation is inhibited or insufficient to trigger cell death.

Role in Disease

Dysregulation of AIF has been implicated in various diseases. Overactivation of AIF can lead to excessive cell death, contributing to neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Conversely, insufficient AIF activity can result in the survival of damaged cells, potentially leading to cancer development.

Mutations in the AIFM1 gene have been associated with a range of human disorders, including mitochondrial encephalomyopathy, X-linked recessive Charcot-Marie-Tooth disease, and other neurodegenerative conditions.

Research and Therapeutic Potential

Research into AIF continues to explore its potential as a therapeutic target. Modulating AIF activity could provide new avenues for the treatment of diseases characterized by excessive or insufficient apoptosis. For instance, inhibiting AIF activity might protect neurons in neurodegenerative diseases, while enhancing its activity could promote the death of cancer cells.

Related pages

• Apoptosis
• Mitochondria
• Caspase
• Bcl-2 family

Gallery

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  Diagram of apoptosis-inducing factor