Related Experiment Video

Updated: Jul 9, 2026

In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice
08:40

In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice

Published on: November 22, 2017

The inositol 1,4,5-trisphosphate receptor is required to signal autophagic cell death

David Lam1, Artemis Kosta, Marie-Françoise Luciani

  • 1Centre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale U631, and Centre National de la Recherche Scientifique Unité Mixte de Recherche 6102, Aix Marseille Université, Marseille, France.

Molecular Biology of the Cell
|December 14, 2007
PubMed

Insights

Researchers identified a key signaling pathway for autophagic cell death (ACD) in Dictyostelium. Inactivation of the inositol 1,4,5-trisphosphate receptor (IP3R) gene prevented ACD, highlighting IP3R

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Autophagic cell death (ACD) and necrotic cell death (NCD) are critical pathophysiological processes with incompletely understood signaling pathways.
  • The Dictyostelium eukaryote model offers unique advantages for studying cell death due to its genetic tractability and lack of apoptotic machinery.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying autophagic cell death (ACD) signaling.
  • To identify novel genes and pathways involved in the differentiation factor DIF-induced ACD in Dictyostelium.

Main Methods:

  • Random insertional mutagenesis was employed to screen for genes affecting ACD.
  • The role of the inositol 1,4,5-trisphosphate receptor (IP3R) in ACD was investigated.
  • The impact of calcium (Ca2+)-related drugs on DIF signaling and ACD was assessed.

Main Results:

  • Inactivation of the iplA gene, encoding the sole IP3R in Dictyostelium, abolished DIF-induced ACD.
  • IP3R, a channel regulating Ca2+ release from the endoplasmic reticulum, is essential for ACD.
  • Ca2+-related drugs modulated DIF signaling, impacting ACD, suggesting a Ca2+-dependent mechanism.

Conclusions:

  • A novel signaling pathway for autophagic cell death (ACD) in Dictyostelium requires the inositol 1,4,5-trisphosphate receptor (IP3R).
  • This pathway involves Ca2+-dependent steps, providing new molecular insights into ACD.
  • This study represents a significant advancement in understanding the molecular basis of autophagic cell death.

More Related Videos

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation06:12

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation

Published on: May 3, 2024

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Related Concept Videos

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...
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...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
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...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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...