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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...
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...
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.
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.
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...
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Updated: Jun 23, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

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Published on: March 5, 2018

Redox-linked conformational dynamics in apoptosis-inducing factor.

Irina F Sevrioukova1

  • 1Department of Molecular Biology and Biochemistry, University of California, Irvine, 92697-3900, USA. sevrioui@uci.edu

Journal of Molecular Biology
|May 19, 2009
PubMed
Summary
This summary is machine-generated.

Apoptosis-inducing factor (AIF) is crucial for cell energy and programmed cell death. Structural studies reveal how NADH binding controls AIF

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Last Updated: Jun 23, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
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Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
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12:55

Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis

Published on: February 16, 2015

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein involved in energy metabolism and caspase-independent apoptosis.
  • The precise function of AIF in healthy mitochondria and its redox mechanism are not fully understood.
  • NADH reduction induces AIF dimerization and formation of functional charge-transfer complexes (CTC).

Purpose of the Study:

  • To elucidate the structure-function relationships of AIF.
  • To gain insight into the redox mechanism of AIF.
  • To understand how NADH binding regulates AIF's normal and apoptotic functions.

Main Methods:

  • X-ray crystallography of oxidized and NADH-reduced murine AIF.
  • Biochemical assays to validate structural findings.

Main Results:

  • Determined X-ray structures of oxidized and NADH-reduced AIF.
  • Identified key stabilizing interactions within the NADH-AIF complex, including pi-stacking and hydrogen bonding involving His453.
  • Observed redox-dependent conformational changes transmitting signals to the protein surface, promoting dimerization and regulating nuclear localization.

Conclusions:

  • NADH binding stabilizes AIF through specific structural interactions, including a His453-mediated conformational switch.
  • Redox-induced structural changes control AIF dimerization and nuclear translocation, impacting both normal mitochondrial function and apoptosis.
  • NADH is a key regulator of both the physiological and apoptogenic roles of AIF.