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

Regulated Protein Degradation

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...

The Proteasome

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...

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,...

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...

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...

Export of Misfolded Proteins out of the ER

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...

You might also read

Related Articles

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

Sort by

Same author

Heatwave Exposure Accelerates Biological Aging via Metabolic Dysregulation.

Cyborg and bionic systems (Washington, D.C.)·2026

Same author

Carrier-Free Nanoassembly Suppresses Phase Separation via Ribosome-Inspired Crowding Control for Enhanced Chemo-Immunotherapy.

ACS nano·2026

Same author

A Single Probe for Two Separate Imaging Applications: Turn-On Labeling of the Cell-Surface Proteome and Wash-Free Detection of Membrane Damage.

Analytical chemistry·2026

Same author

An electrophilicity-engineered magnetic sensor for MRI detection of dormant tumor cell clusters.

Science advances·2026

Same author

Distinct clinical features and epidemiological trends of very early and middle-aged early onset colorectal cancer based on SEER 17 and GBD 2021 data over the past 15 years.

BMC cancer·2025

Same author

A modular artificial intelligence framework to facilitate fluorophore design.

Nature communications·2025

Search research articles

Related Experiment Video

Updated: Jun 5, 2025

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

Autophagy-Mediated Targeted Protein Degradation.

Jinning Shao¹, Shangzhi Xie¹, Shurui Hong¹

¹Institute of Drug Metabolism and Pharmaceutical Analysis, Research Center for Clinical Pharmacy, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.

|December 13, 2024

Summary

Autophagy, a cellular recycling process, is being harnessed for targeted protein degradation (TPD) to eliminate disease-related proteins. This review covers small-molecule and macromolecule strategies for TPD, offering new drug discovery insights.

Keywords:

Autophagy Macromolecule chimera Small molecule Targeted protein degradation

More Related Videos

Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae

Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae

Published on: April 18, 2016

Assaying Proteasomal Degradation in a Cell-free System in Plants

Assaying Proteasomal Degradation in a Cell-free System in Plants

Published on: March 26, 2014

Related Experiment Videos

Last Updated: Jun 5, 2025

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae

Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae

Published on: April 18, 2016

Assaying Proteasomal Degradation in a Cell-free System in Plants

Assaying Proteasomal Degradation in a Cell-free System in Plants

Published on: March 26, 2014

Area of Science:

Cellular Biology
Biochemistry
Drug Discovery

Background:

Autophagy is a fundamental eukaryotic process for cellular component turnover and homeostasis.
Dysfunctional proteins contribute to various diseases.
Targeted protein degradation (TPD) offers a novel therapeutic strategy.

Purpose of the Study:

To introduce the mechanism of autophagy.
To review current small-molecule and macromolecule-based TPD strategies.
To highlight the potential of autophagy-mediated TPD in drug discovery.

Main Methods:

Literature review of autophagy mechanisms.
Analysis of existing TPD strategies.
Discussion of small-molecule and macromolecule-based approaches.

Main Results:

Autophagy facilitates the degradation of cellular components via the lysosome.
TPD strategies leverage autophagy to remove specific disease-related proteins.
Both small molecules and macromolecules can mediate autophagy-based TPD.

Conclusions:

Autophagy-mediated TPD presents a promising avenue for therapeutic intervention.
Targeting intracellular and cell-surface proteins is achievable.
This approach holds significant potential for future drug development.