Related Experiment Video

Updated: Aug 19, 2026

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

Apoptosis-inducing factor is a key factor in neuronal cell death propagated by BAX-dependent and BAX-independent

Eric C C Cheung1, Lysanne Melanson-Drapeau, Sean P Cregan

  • 1Ottawa Health Research Institute, Neuroscience Center and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|February 11, 2005
PubMed

Insights

Apoptosis-inducing factor (AIF) plays a dual role in neuronal injury. This study reveals AIF

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Mitochondria release proteins initiating caspase-dependent and -independent cell death.
  • Apoptosis-inducing factor (AIF) is a key regulator in caspase-independent neuronal death.
  • AIF's role in neuronal injury (oxidative stress, excitotoxicity) remains controversial.

Purpose of the Study:

  • To investigate the role of AIF in BAX-dependent and BAX-independent neuronal death.
  • To evaluate AIF's function in excitotoxicity and DNA damage-induced neuronal injury.

Main Methods:

  • Utilized Harlequin (Hq) mice, which have reduced AIF levels (hypomorphic).
  • Examined double mutant neurons (Hq/Apaf1-/-) lacking functional caspase-dependent and AIF-mediated pathways.
  • Assessed neuronal protection against DNA damage and glutamate-induced excitotoxicity.
  • Conducted in vivo studies using kainic acid-induced seizures in Hq mice.

Main Results:

  • Hq/Apaf1-/- neurons showed enhanced neuroprotection against DNA damage and excitotoxicity.
  • AIF was implicated in NMDA- and kainic acid-induced excitotoxicity, but not AMPA-induced.
  • Hq mice exhibited significantly reduced hippocampal damage following kainic acid-induced seizures compared to wild-type.

Conclusions:

  • AIF is crucial for both BAX-dependent and BAX-independent neuronal injury pathways.
  • AIF contributes to excitotoxic neuronal death, particularly via NMDA and kainic acid.
  • Reducing AIF levels offers neuroprotection in models of neuronal injury.

More Related Videos

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons10:36

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons

Published on: November 6, 2017

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila13:21

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila

Published on: November 27, 2016

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...