Related Experiment Video
Updated: Jul 18, 2025
08:40
Spatial and Temporal Analysis of Active ERK in the C. elegans Germline
Published on: November 29, 2016
10.3K
PINK1, Keap1, and Rtnl1 regulate selective clearance of endoplasmic reticulum during development
Ruoxi Wang1, Tina M Fortier1, Fei Chai1
1Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Cell
|August 26, 2023
Summary
Parkinson
Area of Science:
- Cell Biology
- Autophagy
- Organelle Homeostasis
Background:
- Selective organelle clearance, including endoplasmic reticulum (ER) and mitochondria, via autophagy is vital for cellular health.
- Dysregulation of these processes is implicated in various diseases.
Purpose of the Study:
- To elucidate the molecular mechanisms governing developmentally programmed selective ER clearance by autophagy.
- To investigate the roles of PINK1, Parkin, Keap1, Cullin3, and specific receptors in ER and mitochondrial autophagy.
Main Methods:
- Investigated the function of Parkinson's disease-associated PINK1 and its downstream effectors.
- Utilized genetic and biochemical approaches to analyze protein interactions and ubiquitylation.
- Examined the regulation of ER-phagy receptors Atl, Rtnl1, and Trp1.
Main Results:
- Identified PINK1 as a key regulator of selective ER clearance.
- Demonstrated that Parkin is required for mitochondrial clearance but opposes ER clearance.
- Showed that Keap1 and Cullin3 function downstream of PINK1 to regulate ER clearance by influencing Rtnl1 and Atl.
- Revealed PINK1-mediated Keap1 localization and Rtnl1 ubiquitylation are critical for ER clearance.
Conclusions:
- PINK1 orchestrates selective ER and mitochondrial clearance by balancing Keap1- and Parkin-dependent ubiquitylation.
- This balance determines which organelle is targeted for autophagic removal.
- The findings provide new insights into organelle quality control and its links to neurodegenerative diseases.
Related Concept Videos
01:45Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
01:31Regulation of the Unfolded Protein Response
2.5K
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...
2.5K
01:28The Early Endosome: Endocytosis of Transferrin
3.3K
Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
3.3K
01:45ER Retrieval Pathway
3.9K
In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
3.9K
01:29Protein Folding Quality Check in the RER
3.7K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
3.7K
01:23Negative Regulator Molecules
35.4K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.4K