Related Experiment Video

Updated: Feb 2, 2026

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila
13:21

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila

Published on: November 27, 2016

9.5K

The Mitochondrial Apoptotic Effectors BAX/BAK Activate Caspase-3 and -7 to Trigger NLRP3 Inflammasome and Caspase-8

James E Vince1, Dominic De Nardo1, Wenqing Gao2

  • 1The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.

Cell Reports
|November 29, 2018
PubMed

Insights

Intrinsic apoptosis, typically silent, activates IL-1β in macrophages via BAX/BAK signaling. This pathway involves caspase-8 and NLRP3 inflammasome, revealing inflammatory potential in apoptotic innate immune cells.

Area of Science:

  • Immunology
  • Cellular Biology
  • Molecular Medicine

Background:

  • Intrinsic apoptosis, driven by BAX/BAK, was considered immunologically silent.
  • Understanding immune responses during apoptosis is crucial for diseases like cancer.

Purpose of the Study:

  • To investigate the immunological consequences of BAX/BAK-mediated apoptosis in macrophages.
  • To elucidate the molecular mechanisms linking apoptosis to pro-inflammatory cytokine release.

Main Methods:

  • Utilized macrophage models to study BAX/BAK activation and its downstream effects.
  • Investigated protein degradation pathways, including inhibitor of apoptosis (IAP) proteins.
  • Analyzed caspase activation (caspase-8, -3, -7, -1) and inflammasome signaling (NLRP3).
  • Assessed the role of potassium efflux and pyroptosis effectors (gasdermin D/E) in IL-1β release.

Main Results:

  • BAX/BAK activation in macrophages leads to IAP degradation, promoting caspase-8-mediated IL-1β activation.
  • BAX/BAK signaling triggers a parallel pathway for IL-1β maturation via the NLRP3 inflammasome, dependent on potassium efflux.
  • Apoptotic caspases (-3, -7) function upstream of both caspase-8 and NLRP3 inflammasome pathways for IL-1β maturation and secretion.
  • Gasdermin D and E are not required for BAX/BAK-induced IL-1β release, distinguishing it from pyroptosis.

Conclusions:

  • BAX/BAK-mediated apoptosis in innate immune cells can generate pro-inflammatory signals, specifically IL-1β.
  • This mechanism explains IL-1β activation observed during cellular stress, such as chemotherapy.
  • The findings challenge the paradigm of immunologically silent apoptosis and highlight a novel inflammatory role for intrinsic apoptosis.
Keywords:
BAKBAXBCL-XLGasderminIAPsMCL-1NLRP3caspase-1caspase-8mitochondria

More Related Videos

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells09:04

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

21.4K
Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

3.8K

Related Concept Videos

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...
13.9K
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH301:11

ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3

All ortho–para directors, excluding halogens, are activating groups. These groups donate electrons to the ring, making the ring carbons electron-rich. Consequently, the reactivity of the aromatic ring towards electrophilic substitution increases. For instance, the nitration of anisole is about 10,000 times faster than the nitration of benzene. The electron-donating effect of the methoxy group in anisole activates the ortho and para positions on the ring and stabilizes the corresponding...
7.5K
tRNA Activation02:26

tRNA Activation

Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...
22.9K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
8.6K
Activation Energy01:26

Activation Energy

Activation energy is the minimum amount of energy necessary for a chemical reaction to move forward. The higher the activation energy, the slower the rate of the reaction. However, adding heat to the reaction will increase the rate, since it causes molecules to move faster and increase the likelihood that molecules will collide. The collision and breaking of bonds represents the uphill phase of a reaction and generates the transition state. The transition state is an unstable high-energy state...
86.6K
Eukaryotic Transcription Activators02:42

Eukaryotic Transcription Activators

Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
12.8K