Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Receptor Downregulation in MVBs

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...

Autophagy

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...

PI3K/mTOR/AKT Signaling Pathway

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...

Autophagic Cell Death

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...

Delivery Pathways to the Lysosome

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...

NF-κB-dependent Signaling Pathway

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

The ubiquitin-proteasome system and autophagy as guardians of the cellular proteome.

FEBS letters·2026

Same author

Intracellular lipopolysaccharide binds RETREG1/FAM134B to regulate ER remodeling upon bacterial infection.

Autophagy·2026

Same author

Targeting ubiquitin signaling vulnerabilities in KEAP1-inactivated lung cancer.

The EMBO journal·2026

Same author

Author Correction: Ubiquitination and autophagy in host-pathogen interactions: from immune surveillance to therapeutic targeting.

Nature reviews. Immunology·2026

Same author

Author Correction: Multi-scale classification decodes the complexity of the human E3 ligome.

Nature communications·2026

Same author

DNA-protein cross-links promote cGAS-STING-driven premature aging and embryonic lethality.

Science (New York, N.Y.)·2026

Search research articles

Related Experiment Video

Updated: May 15, 2026

Cell-Based Drug Screening for Inhibitors of Autophagy Related 4B Cysteine Peptidase

Cell-Based Drug Screening for Inhibitors of Autophagy Related 4B Cysteine Peptidase

Published on: June 30, 2023

TBK1 restricts IRGQ-mediated autophagy.

Uxia Gestal-Mato¹, Pauline Lascaux¹, Sergio Alejandro Poveda-Cuevas^1,2

¹Institute of Biochemistry II, Medical Faculty, Goethe University Frankfurt, Frankfurt am Main, Germany.

Nature Communications

|May 13, 2026

Summary

The autophagy receptor IRGQ, interacting with GABARAPL2, acts as a hub for autophagy initiation. TBK1 activation disrupts this complex, reducing specific autophagic flux without impacting bulk autophagy.

More Related Videos

Study of Protein-protein Interactions in Autophagy Research

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

Published on: January 31, 2025

Related Experiment Videos

Last Updated: May 15, 2026

Cell-Based Drug Screening for Inhibitors of Autophagy Related 4B Cysteine Peptidase

Cell-Based Drug Screening for Inhibitors of Autophagy Related 4B Cysteine Peptidase

Published on: June 30, 2023

Study of Protein-protein Interactions in Autophagy Research

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

Published on: January 31, 2025

Area of Science:

Cellular Biology
Molecular Biology
Autophagy Research

Background:

The autophagy-lysosome system is crucial for degrading cellular components like damaged organelles and pathogens.
Autophagy receptors, such as IRGQ, play key roles in cargo recognition and delivery for degradation.
The hATG8 family proteins are essential mediators in the autophagy pathway.

Purpose of the Study:

To investigate the role of the autophagy receptor IRGQ and its interaction with GABARAPL2 in regulating autophagic flux.
To elucidate the mechanism by which TBK1 regulates the IRGQ-GABARAPL2 complex.
To understand how this regulation impacts the initiation of autophagy and cargo-specific degradation.

Main Methods:

Proteomic analysis to identify protein interactions.
Biochemical assays to confirm binding affinities and regulatory mechanisms.
High-throughput microscopy to visualize and quantify autophagic processes in live cells.

Main Results:

The IRGQ-GABARAPL2 complex serves as a critical interaction hub between hATG8s and autophagy initiation factors, promoting lipidation and autophagic flux.
TBK1 activation leads to GABARAPL2 phosphorylation at S10, disrupting the IRGQ-GABARAPL2 complex.
This disruption reduces the autophagic flux of GABARAPL2 and IRGQ-bound cargo, while bulk autophagy remains unaffected.

Conclusions:

IRQG functions as a regulated interaction hub for autophagy initiation.
TBK1 negatively regulates this hub through phosphorylation of GABARAPL2, thereby controlling specific autophagic pathways.
These findings expand the understanding of IRGQ's function and the intricate regulation of selective autophagy.