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

Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

5.1K
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...
5.1K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

9.8K
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,...
9.8K
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

3.2K
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...
3.2K
Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

4.4K
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...
4.4K
Nuclear Protein Sorting01:34

Nuclear Protein Sorting

5.7K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
5.7K
Export of Mitochondrial and Chloroplast Genes02:19

Export of Mitochondrial and Chloroplast Genes

3.9K
A eukaryotic cell can have up to three different types of genetic systems: nuclear, mitochondrial, and chloroplast. During evolution, organelles have exported many genes to the nucleus; this transfer is still ongoing in some plant species. Approximately 18% of the Arabidopsis thaliana nuclear genome is thought to be derived from the chloroplast’s cyanobacterial ancestor, and around 75% of the yeast genome derived from the mitochondria’s bacterial ancestor. This export has occurred...
3.9K

You might also read

Related Articles

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

Sort by
Same author

Mitochondrial-derived compartments buffer outer membrane protein load during acute mitochondrial adaptation.

bioRxiv : the preprint server for biology·2026
Same author

Vacuole pH loss triggers ESCRT-dependent plasma membrane remodeling to prevent amino acid toxicity.

bioRxiv : the preprint server for biology·2026
Same author

Deficits in mitochondrial dynamics and iron balance result in templated insertions.

Nature communications·2025
Same author

Mitochondrial-derived compartments remove surplus proteins from the outer mitochondrial membrane.

The Journal of cell biology·2024
Same author

Mitochondrial-derived compartments are multilamellar domains that encase membrane cargo and cytosol.

The Journal of cell biology·2024
Same author

The phospholipids cardiolipin and phosphatidylethanolamine differentially regulate MDC biogenesis.

The Journal of cell biology·2024

Related Experiment Video

Updated: Nov 12, 2025

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

A nuclear-based quality control pathway for non-imported mitochondrial proteins.

Viplendra Ps Shakya1, William A Barbeau1, Tianyao Xiao1

  • 1Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.

Elife
|March 18, 2021
PubMed
Summary

Cells degrade mis-localized mitochondrial proteins in the nucleus via nuclear-associated mitoprotein degradation (mitoNUC). This pathway, involving specific E3 ligases, prevents toxic protein buildup during mitochondrial dysfunction.

Keywords:
S. cerevisiaecell biologymitochondrianucleusproteasomeprotein importprotein quality control

More Related Videos

Assessment of Submitochondrial Protein Localization in Budding Yeast Saccharomyces cerevisiae
08:55

Assessment of Submitochondrial Protein Localization in Budding Yeast Saccharomyces cerevisiae

Published on: July 19, 2021

3.1K
Author Spotlight: High-Throughput Image-Based Quantification of Mitochondrial DNA Synthesis and Distribution
10:47

Author Spotlight: High-Throughput Image-Based Quantification of Mitochondrial DNA Synthesis and Distribution

Published on: May 5, 2023

4.1K

Related Experiment Videos

Last Updated: Nov 12, 2025

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
Assessment of Submitochondrial Protein Localization in Budding Yeast Saccharomyces cerevisiae
08:55

Assessment of Submitochondrial Protein Localization in Budding Yeast Saccharomyces cerevisiae

Published on: July 19, 2021

3.1K
Author Spotlight: High-Throughput Image-Based Quantification of Mitochondrial DNA Synthesis and Distribution
10:47

Author Spotlight: High-Throughput Image-Based Quantification of Mitochondrial DNA Synthesis and Distribution

Published on: May 5, 2023

4.1K

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Mitochondrial import deficiency leads to cellular toxicity from accumulated mis-localized proteins, known as mitoprotein-induced stress.
  • Cellular systems for degrading these mis-localized mitochondrial precursors are not fully understood.

Purpose of the Study:

  • To identify the cellular location and abundance of mitochondrial precursor proteins during mitochondrial impairment in *Saccharomyces cerevisiae*.
  • To elucidate the degradation pathways for non-imported mitochondrial proteins.

Main Methods:

  • Cataloging the location and steady-state abundance of mitochondrial precursor proteins in yeast under mitochondrial stress.
  • Investigating the role of the nucleus and proteasome in the degradation of these proteins.

Main Results:

  • Non-imported mitochondrial proteins were found to localize to the nucleus.
  • A novel degradation pathway, nuclear-associated mitoprotein degradation (mitoNUC), was identified, involving proteasome-dependent breakdown.
  • mitoNUC requires an N-terminal mitochondrial targeting sequence and is mediated by E3 ubiquitin ligases San1, Ubr1, and Doa10.
  • Impaired degradation resulted in sequestration of precursors in nuclear-associated foci.

Conclusions:

  • The nucleus serves as a critical site for the disposal of non-imported mitochondrial precursor proteins.
  • The mitoNUC pathway is essential for managing mitochondrial precursor protein accumulation and preventing cellular toxicity.