Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

13.7K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
13.7K
The Proteasome Structure01:17

The Proteasome Structure

2.1K
The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...
2.1K
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

3.9K
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
3.9K
Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

5.1K
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
5.1K
The Proteasome02:18

The Proteasome

10.5K
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...
10.5K
The Proteasome01:13

The Proteasome

2.0K
Eukaryotic cells can degrade proteins through several pathways. One of the most important among 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. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
2.0K

You might also read

Related Articles

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

Sort by
Same author

On-filter fractionation by empFASP improves identification of membrane peptides in proteomic experiments.

Journal of proteomics·2026
Same author

Rhomboid protease Rhbdl2 regulates macrophage recruitment and wound regeneration in zebrafish.

bioRxiv : the preprint server for biology·2026
Same author

Targeting the Membrane-Embedded Rhomboid Protease GlpG: A Multimodal Strategy for Inhibitor Discovery and Mechanistic Insight.

Angewandte Chemie (International ed. in English)·2026
Same author

Engineering cardiolipin binding to an artificial membrane protein reveals determinants for lipid-mediated stabilization.

eLife·2025
Same author

An in vitro platform for the enzymatic characterization of the rhomboid protease RHBDL4.

The Journal of biological chemistry·2025
Same author

4-Oxo-β-lactams as Covalent Inhibitors of the Mitochondrial Intramembrane Protease PARL.

ACS medicinal chemistry letters·2024

Related Experiment Video

Updated: Mar 28, 2026

Determining Membrane Protein Topology Using Fluorescence Protease Protection FPP
08:14

Determining Membrane Protein Topology Using Fluorescence Protease Protection FPP

Published on: April 20, 2015

18.4K

Why cells need intramembrane proteases - a mechanistic perspective.

Kvido Strisovsky1

  • 1Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.

The FEBS Journal
|December 31, 2015
PubMed
Summary

Intramembrane proteases (IMPRs) cleave proteins within cell membranes. This review explores how IMPRs recognize substrates, focusing on rhomboid proteases, to understand their evolution and function.

Keywords:
enzyme mechanismintramembrane proteasemembrane proteinrhomboid proteasesubstrate specificity

More Related Videos

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches
05:56

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches

Published on: October 13, 2022

1.9K
Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

9.5K

Related Experiment Videos

Last Updated: Mar 28, 2026

Determining Membrane Protein Topology Using Fluorescence Protease Protection FPP
08:14

Determining Membrane Protein Topology Using Fluorescence Protease Protection FPP

Published on: April 20, 2015

18.4K
Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches
05:56

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches

Published on: October 13, 2022

1.9K
Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

9.5K

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Evolutionary Biology

Background:

  • Intramembrane proteases (IMPRs) are enzymes that cleave transmembrane proteins within the lipid bilayer.
  • Their roles in diverse biological processes are increasingly recognized, yet their evolutionary and functional significance is still being uncovered.
  • While structures of key IMPR families exist, substrate recognition and cleavage mechanisms remain poorly understood.

Purpose of the Study:

  • To provide an overview of substrate recognition by IMPRs, viewed through the lens of their biological functions.
  • To focus on rhomboid proteases to elucidate emerging principles and ongoing debates in the field.
  • To argue that understanding IMPR mechanisms, specificity, and substrate repertoires is key to comprehending their evolutionary selection.

Main Methods:

  • Review of existing literature on intramembrane proteases and rhomboid proteases.
  • Analysis of biological functions to infer substrate recognition principles.
  • Comparative analysis of IMPR families and their natural substrates.

Main Results:

  • Emerging principles of substrate recognition by IMPRs are being delineated, particularly within the rhomboid protease family.
  • Areas of scientific contention regarding IMPR mechanisms and specificity are highlighted.
  • The study emphasizes the link between biological function, evolutionary selection, and IMPR properties.

Conclusions:

  • Studying IMPR mechanisms, specificity, and natural substrate repertoires is crucial for understanding their evolutionary trajectory.
  • Rhomboid proteases serve as a key model for understanding broader IMPR substrate recognition.
  • Further research into IMPR function and evolution will illuminate the selective pressures shaping these unique enzymes.