Role for apoptosis-inducing factor in the physiological death of cerebellar neurons

Sugela Blancas1, Julio Moran

  • 1Neuroscience Division, Institute of Cell Physiology, National Autonomous University of Mexico, Mexico City, Mexico.

Insights

Apoptosis-inducing factor (AIF) plays a role in neuronal death during cerebellar development. AIF contributes to caspase-dependent and independent cell death pathways in cerebellar granule neurons.

Area of Science:

  • Neuroscience
  • Cell Biology

Background:

  • Apoptosis-inducing factor (AIF) is involved in caspase-independent cell death.
  • AIF translocates from mitochondria to the nucleus, inducing chromatin condensation and DNA degradation.

Purpose of the Study:

  • To investigate the role of AIF in neuronal death under physiological conditions.
  • To examine AIF's involvement in cerebellar granule neuron (CGN) death induced by low potassium (K5).

Main Methods:

  • Analysis of AIF cellular localization during cerebellar development.
  • Culture of CGN in low potassium (5 mM) and treatment with caspase inhibitors.
  • Assessment of cell death markers like phosphatidylserine translocation and nuclear condensation.

Main Results:

  • Nuclear AIF localization increased with age during cerebellar development.
  • K5 induced caspase-dependent CGN death with late nuclear AIF translocation.
  • Caspase inhibition only slightly reduced K5-induced CGN death, with increased nuclear AIF.

Conclusions:

  • AIF is implicated in K5-induced apoptotic-like death of CGN.
  • AIF may represent an alternative neuronal death mechanism during cerebellar development.

Related Concept Videos

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...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
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.
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...
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...