AIFM - Apoptosis inducing factor mitochondria associated | Elisa - Clia - Antibody - Protein

Background:

Apoptosis-Inducing Factor Mitochondria-Associated (AIFM) refers to a group of proteins associated with mitochondria that share structural and functional similarities with the classical apoptosis-inducing factor (AIF). AIFM proteins are involved in regulating apoptosis, similar to the classical AIF. They primarily function within the mitochondria, participating in various cellular processes such as oxidative phosphorylation, reactive oxygen species (ROS) production, and apoptosis induction. Like AIF, AIFM proteins can induce cell death through both caspase-dependent and caspase-independent pathways. In the caspase-independent pathway, AIFM proteins are released from mitochondria into the cytoplasm in response to cellular stress, where they translocate to the nucleus and induce chromatin condensation and DNA fragmentation, ultimately leading to cell death. In addition to their role in apoptosis, AIFM proteins contribute to maintaining mitochondrial function and integrity. They participate in processes such as electron transport chain regulation, mitochondrial dynamics, and mitochondrial DNA maintenance.Mutations in the AIFM1 gene are correlated with Charcot-Marie-Tooth disease (Cowchock syndrome). (hereditary motor and sensory neuropathy of the peripheral nervous system characterized by progressive loss of muscle tissue)

Protein Structure:

• Molecular Weight: Approximately 67 kDa.
• Primary Structure: Composed of 613 amino acids.
• Domains: AIFM contains a mitochondrial localization signal at the N-terminus, a FAD-binding domain, and a C-terminal apoptotic domain.
• Post-translational Modifications: AIFM undergoes proteolytic cleavage to produce a truncated form that translocates to the nucleus during apoptosis.

Classification and Subtypes:

• Protein Family: AIFM belongs to the NADH oxidase/flavin oxidoreductase family.
• Isoforms: There are different isoforms of AIFM generated through alternative splicing, including AIFM1, which is the primary form involved in apoptosis.

Function and Biological Significance:

• Apoptosis Induction: In response to apoptotic stimuli, AIFM is released from the mitochondria into the cytoplasm and then translocates to the nucleus, where it induces chromatin condensation and large-scale DNA fragmentation, facilitating caspase-independent apoptosis.
• Mitochondrial Function: AIFM maintains mitochondrial structure and function, supporting oxidative phosphorylation and managing reactive oxygen species (ROS) levels.
• Cell Survival: Beyond its role in apoptosis, AIFM is critical for cell survival by maintaining mitochondrial bioenergetics and preventing excessive oxidative stress.

Interactions:

• PARP1 (Poly ADP-Ribose Polymerase 1): During apoptosis, activation of PARP1 leads to AIFM release from mitochondria.
• Endonuclease G: AIFM collaborates with endonuclease G to mediate DNA fragmentation in the nucleus during apoptosis.
• CYP450 (Cytochrome P450): AIFM interacts with mitochondrial cytochrome P450 enzymes, influencing electron transport and oxidative stress responses.

Clinical Issues:

• Neurodegenerative Diseases: Dysfunctional AIFM activity and mitochondrial impairment are linked to neurodegenerative conditions like Parkinson's and Alzheimer's diseases.
• Cancer: AIFM's role in regulating apoptosis makes it a significant focus in cancer research, where its modulation could affect tumor cell survival and apoptosis.
• Ischemia-Reperfusion Injury: AIFM is implicated in cell death during ischemia-reperfusion injury, such as in myocardial infarction and stroke, highlighting its potential as a therapeutic target.

Summary:

AIFM (Apoptosis Inducing Factor Mitochondria Associated) is a pivotal protein involved in caspase-independent apoptosis and mitochondrial function. It ensures cell survival under normal conditions by maintaining mitochondrial integrity and energy production. During apoptosis, AIFM translocates to the nucleus to induce DNA fragmentation and chromatin condensation. Its dysregulation is associated with various diseases, including neurodegenerative disorders and cancer, making it a vital target for therapeutic interventions. Understanding AIFM's mechanisms and interactions provides crucial insights into potential treatments for these conditions.