Related Experiment Video

Updated: Feb 18, 2026

Study of Endoplasmic Reticulum and Mitochondria Interactions by In Situ Proximity Ligation Assay in Fixed Cells
09:34

Study of Endoplasmic Reticulum and Mitochondria Interactions by In Situ Proximity Ligation Assay in Fixed Cells

Published on: December 10, 2016

25.5K

Receptor-mediated Drp1 oligomerization on endoplasmic reticulum

Wei-Ke Ji1,2, Rajarshi Chakrabarti1, Xintao Fan1

  • 1Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH.

The Journal of Cell Biology
|November 22, 2017
PubMed

Insights

The endoplasmic reticulum (ER) acts as a platform for Drp1 guanosine triphosphatase (GTPase) oligomerization, facilitating mitochondrial division. This ER-associated Drp1 is crucial for regulating mitochondrial and peroxisomal division processes.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Dynamin-related protein 1 (Drp1) is essential for mitochondrial and peroxisomal division.
  • Endoplasmic reticulum (ER) and actin filaments are known to positively influence mitochondrial division, but their mechanisms are unclear.
  • Drp1 recruitment and oligomerization are regulated by mitochondrial receptors like Mff, MiD49, MiD51, and Fis1.

Purpose of the Study:

  • To investigate the role of the endoplasmic reticulum (ER) in Drp1 oligomerization and mitochondrial division.
  • To elucidate the mechanisms by which ER influences Drp1-mediated organelle division.

Main Methods:

  • Immunofluorescence microscopy to visualize Drp1, Mff, and Fis1 localization on ER, mitochondria, and peroxisomes.
  • Cellular assays to assess Drp1 oligomerization and mitochondrial division.
  • Genetic manipulation, including suppression of Mff and inhibition of actin polymerization via INF2.

Main Results:

  • A distinct population of Drp1 oligomers was found associated with the ER in mammalian cells.
  • Subpopulations of Mff and Fis1 were also localized to the ER.
  • Suppression of Mff or inhibition of actin polymerization reduced all Drp1 oligomer populations and mitochondrial division.
  • Targeting Mff to the ER stimulated mitochondrial division.

Conclusions:

  • The ER serves as a platform for Drp1 oligomerization.
  • ER-associated Drp1 contributes significantly to mitochondrial division.
  • Mff and actin filaments, potentially via INF2, play critical roles in regulating Drp1 assembly and function on the ER for organelle division.

More Related Videos

Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells16:43

Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells

Published on: February 18, 2014

13.7K
Using Scaffold Liposomes to Reconstitute Lipid-proximal Protein-protein Interactions In Vitro08:53

Using Scaffold Liposomes to Reconstitute Lipid-proximal Protein-protein Interactions In Vitro

Published on: January 11, 2017

9.4K

Related Concept Videos

Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
18.0K
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...
3.1K
Receptor-mediated Endocytosis01:38

Receptor-mediated Endocytosis

Overview
111.8K
Receptor-mediated Endocytosis01:20

Receptor-mediated Endocytosis

Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
8.2K
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.5K
ER Retrieval Pathway01:45

ER Retrieval Pathway

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...
4.9K