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

Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

3.6K
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...
3.6K
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

4.2K
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...
4.2K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

3.0K
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,...
3.0K
Energy to Drive Translocation01:37

Energy to Drive Translocation

2.0K
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
2.0K
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

2.5K
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...
2.5K
Mitochondrial Membranes01:45

Mitochondrial Membranes

8.1K
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,...
8.1K

You might also read

Related Articles

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

Sort by
Same author

Intracellular vesicle-mediated biomineralization of arsenic and barium by a sponge symbiotic bacterium.

ISME communications·2026
Same author

Structural remodeling of the mitochondrial protein biogenesis machinery under proteostatic stress.

Science advances·2026
Same author

Structural basis for ATP-driven double-ring assembly of the human mitochondrial Hsp60 chaperonin.

bioRxiv : the preprint server for biology·2025
Same author

Epidemiology of the Crimean-Congo hemorrhagic fever virus.

Acta tropica·2025
Same author

Scheimpflug Imaging in Isolated Ectopia Lentis.

Ophthalmology·2025
Same author

Identification of Natural Compounds as Potential COVID-19 Main Protease (Mpro) Inhibitors: A Comprehensive Study and <i>In silico</i> Evidence.

Current pharmaceutical design·2025

Related Experiment Video

Updated: Jun 3, 2025

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

2.8K

Hotspots for Disease-Causing Mutations in the Mitochondrial TIM23 Import Complex.

Sahil Jain1,2, Eyal Paz1, Abdussalam Azem1,3

  • 1School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.

Genes
|January 8, 2025
PubMed
Summary
This summary is machine-generated.

Mitochondrial protein import relies on the TIM23 complex. Mutations in TIM23 components, especially Tim50, cause early-onset developmental and neurological diseases.

Keywords:
TIM23 complexTimm50mitochondrial protein importrare genetic disorders

More Related Videos

Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing
07:24

Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing

Published on: February 10, 2023

1.4K
Author Spotlight: Transmitochondrial Cybrid Generation Using Cancer Cell Lines
07:49

Author Spotlight: Transmitochondrial Cybrid Generation Using Cancer Cell Lines

Published on: March 17, 2023

2.3K

Related Experiment Videos

Last Updated: Jun 3, 2025

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

2.8K
Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing
07:24

Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing

Published on: February 10, 2023

1.4K
Author Spotlight: Transmitochondrial Cybrid Generation Using Cancer Cell Lines
07:49

Author Spotlight: Transmitochondrial Cybrid Generation Using Cancer Cell Lines

Published on: March 17, 2023

2.3K

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • The human mitochondrial proteome consists of ~1500 proteins, with most encoded by the nuclear genome and imported into mitochondria.
  • Mitochondrial protein import is a complex process involving multiple protein complexes across four mitochondrial compartments.

Purpose of the Study:

  • This mini-review focuses on the translocase of the inner membrane 23 (TIM23) complex, crucial for importing ~60% of mitochondrial proteins.
  • It examines pathogenic mutations in TIM23 complex genes and their link to early-onset diseases.

Main Methods:

  • Review of existing literature on mitochondrial protein import and the TIM23 complex.
  • Analysis of reported pathogenic mutations in genes encoding TIM23 components and associated motor subunits.

Main Results:

  • The TIM23 complex facilitates the import of matrix, inner membrane, and intermembrane space proteins.
  • Numerous pathogenic mutations in TIM23 component genes lead to developmental and neurological defects.

Conclusions:

  • The gene for Tim50 appears to be a mutation hotspot within the core TIM23 complex.
  • Genes for mitochondrial Hsp70 (mortalin) and its J domain regulators are hotspots for mutations affecting presequence translocase-associated motor (PAM) subunits.
  • Disease-causing mutations impact TIM23 complex function, particularly Tim50's role.