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

4.4K
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,...
4.4K
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

4.4K
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
4.4K
The Inner Mitochondrial Membrane01:28

The Inner Mitochondrial Membrane

3.7K
The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria.  In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
3.7K
Mitochondrial Membranes01:45

Mitochondrial Membranes

12.5K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
12.5K
Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

4.1K
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...
4.1K
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

2.6K
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...
2.6K

You might also read

Related Articles

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

Sort by
Same author

A CDK1 phospho-switch reprograms TRAIP to unload replisomes in mitosis.

Science (New York, N.Y.)·2026
Same author

Hetero-oligomerization drives structural plasticity of eukaryotic peroxiredoxins.

Nature chemical biology·2026
Same author

Mitotic BLM functions are required to maintain genomic stability.

Nucleic acids research·2026
Same author

Mitochondrial presequences are more than just address labels.

Protein science : a publication of the Protein Society·2026
Same author

Protein buffering of aneuploidy is driven by coordinated factors identified through machine learning.

Molecular systems biology·2026
Same author

The ribosome-associated complex regulates cytosolic translation upon mitoprotein-induced stress.

The FEBS journal·2025

Related Experiment Video

Updated: Sep 19, 2025

Reconstitution of Msp1 Extraction Activity with Fully Purified Components
05:52

Reconstitution of Msp1 Extraction Activity with Fully Purified Components

Published on: August 10, 2021

2.6K

Dysfunctional mitochondria trap proteins in the intermembrane space.

Tamara Flohr1, Markus Räschle2, Johannes M Herrmann3

  • 1Cell Biology, University of Kaiserslautern, Kaiserslautern, Germany.

The EMBO Journal
|June 16, 2025
PubMed
Summary

Cells have a novel quality control mechanism called mitochondrial triage of precursor proteins (MitoTraP) that sequesters mislocalized mitochondrial proteins. This prevents toxic cytosolic accumulation and protects cellular proteostasis during mitochondrial dysfunction.

Keywords:
Intermembrane SpaceMitochondriaNucleolusProtein TargetingRibosome

More Related Videos

Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue
09:27

Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue

Published on: March 23, 2015

39.8K
Measurement of Protein Import Capacity of Skeletal Muscle Mitochondria
09:01

Measurement of Protein Import Capacity of Skeletal Muscle Mitochondria

Published on: January 7, 2022

2.8K

Related Experiment Videos

Last Updated: Sep 19, 2025

Reconstitution of Msp1 Extraction Activity with Fully Purified Components
05:52

Reconstitution of Msp1 Extraction Activity with Fully Purified Components

Published on: August 10, 2021

2.6K
Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue
09:27

Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue

Published on: March 23, 2015

39.8K
Measurement of Protein Import Capacity of Skeletal Muscle Mitochondria
09:01

Measurement of Protein Import Capacity of Skeletal Muscle Mitochondria

Published on: January 7, 2022

2.8K

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitochondrial dysfunction leads to cytosolic accumulation of precursor proteins, compromising cellular proteostasis and disease.
  • The toxicity of non-imported precursors and cellular defense mechanisms remain poorly understood.

Purpose of the Study:

  • To investigate how eukaryotic cells prevent the accumulation of non-imported mitochondrial precursor proteins in the cytosol.
  • To identify the mechanisms underlying cellular proteostasis during mitochondrial dysfunction.

Main Methods:

  • Utilized a proximity labeling-based assay to monitor the intramitochondrial localization of proteins.
  • Investigated the role of mitochondrial triage of precursor proteins (MitoTraP) in protein localization.

Main Results:

  • Mitochondrial dysfunction causes sequestration of mitochondrial matrix proteins in the intermembrane space (IMS) via MitoTraP.
  • MitoTraP specifically directs matrix proteins, including mitoribosomal proteins, into the IMS.
  • Sequestration of Mrp17 (bS6m) in the IMS prevents its nuclear mistargeting and potential interference with cytosolic ribosome assembly.

Conclusions:

  • MitoTraP is a novel eukaryotic quality control mechanism protecting the proteome from toxic non-imported mitochondrial proteins.
  • This mechanism safeguards cellular proteostasis by preventing aberrant protein localization during mitochondrial stress.