Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Mitochondrial Protein Sorting

Mitochondrial Protein Sorting

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...

Translocation of Proteins into the Mitochondria

Translocation of Proteins into the Mitochondria

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,...

Protein Transport into the Inner Mitochondrial Membrane

Protein Transport into the Inner Mitochondrial Membrane

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...

Porin Insertion in the Outer Mitochondrial Membrane

Porin Insertion in the Outer Mitochondrial Membrane

Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...

Mitochondrial Precursor Proteins

Mitochondrial Precursor Proteins

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...

The Inner Mitochondrial Membrane

The Inner Mitochondrial Membrane

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...

You might also read

Related Articles

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

Sort by

Same author

Identification of candidate cardiomyopathy modifier genes through genome sequencing and RNA profiling.

Frontiers in cardiovascular medicine·2025

Same author

Sensory-Motor Neuropathy in Mfn2 T105M Knock-in Mice and Its Reversal by a Novel Piperine-Derived Mitofusin Activator.

The Journal of pharmacology and experimental therapeutics·2024

Same author

Correction: Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy.

Cell death & disease·2024

Same author

A human mitofusin 2 mutation can cause mitophagic cardiomyopathy.

eLife·2023

Same author

Correction: Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy.

Cell death & disease·2023

Same author

Correction: Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy.

Cell death & disease·2023

Search research articles

Related Experiment Video

Updated: Dec 23, 2025

Author Spotlight: Unveiling Mitochondrial Contact Sites and Architectural Insights

Author Spotlight: Unveiling Mitochondrial Contact Sites and Architectural Insights

Published on: June 16, 2023

Mitofusins as mitochondrial anchors and tethers.

Gerald W Dorn¹

¹Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Journal of Molecular and Cellular Cardiology

|April 19, 2020

Summary

Mitofusins (MFN) tether mitochondria, influencing fusion, motility, and organelle interactions. Their roles as anchoring proteins are crucial for cellular health, with differing impacts in mice versus humans.

Keywords:

Metabolism Mitochondrial dynamics Mitochondrial fusion Mitochondrial transport Mitophagy

More Related Videos

A Model Membrane Platform for Reconstituting Mitochondrial Membrane Dynamics

A Model Membrane Platform for Reconstituting Mitochondrial Membrane Dynamics

Published on: September 2, 2020

Reconstitution of Msp1 Extraction Activity with Fully Purified Components

Reconstitution of Msp1 Extraction Activity with Fully Purified Components

Published on: August 10, 2021

Related Experiment Videos

Last Updated: Dec 23, 2025

Author Spotlight: Unveiling Mitochondrial Contact Sites and Architectural Insights

Author Spotlight: Unveiling Mitochondrial Contact Sites and Architectural Insights

Published on: June 16, 2023

A Model Membrane Platform for Reconstituting Mitochondrial Membrane Dynamics

A Model Membrane Platform for Reconstituting Mitochondrial Membrane Dynamics

Published on: September 2, 2020

Reconstitution of Msp1 Extraction Activity with Fully Purified Components

Reconstitution of Msp1 Extraction Activity with Fully Purified Components

Published on: August 10, 2021

Area of Science:

Cell Biology
Mitochondrial Dynamics
Organelle Interactions

Background:

Mitochondria, with their own genomes, interact with their environment via the outer mitochondrial membrane.
Mitofusins (MFN) are key outer membrane proteins mediating mitochondrial and organelle interactions.

Purpose of the Study:

To review the roles of mitofusins (MFN1 and MFN2) in the heart and other organs.
To examine MFNs as tethers for mitochondria-mitochondria and mitochondria-organelle connections.
To explore MFNs as anchoring proteins for macromolecular complexes.

Main Methods:

Review of existing literature on MFN1 and MFN2 functions.
Analysis of MFN-mediated tethering and anchoring consequences.
Exploration of pathophysiological implications and comparative analysis of mouse vs. human MFN studies.

Main Results:

MFNs tether mitochondria to each other and to other organelles, impacting fusion, motility, mitophagy, and ER calcium cross-talk.
MFN-mediated tethering and anchoring have broad cellular consequences.
Mouse MFN knockout studies reveal severe multi-system phenotypes, contrasting with limited scope in human MFN-linked diseases.

Conclusions:

Mitofusins function primarily as tethering and anchoring proteins, influencing multiple mitochondrial processes.
Understanding MFNs' common functioning provides insight into cellular dynamics.
Discrepancies in MFN knockout phenotypes between mice and humans warrant further investigation.