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Related Concept Videos

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...
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Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

3.2K
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,...
3.2K
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
Energy to Drive Translocation01:37

Energy to Drive Translocation

2.1K
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...
2.1K
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
Porin Insertion in the Outer Mitochondrial Membrane01:12

Porin Insertion in the Outer Mitochondrial Membrane

3.3K
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...
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Assessment of Submitochondrial Protein Localization in Budding Yeast Saccharomyces cerevisiae
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Assessment of Submitochondrial Protein Localization in Budding Yeast Saccharomyces cerevisiae

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Dynamic TOM-TIM23 supercomplex directs mitochondrial protein translocation and sorting.

Yuqi Yang1, Shanshan Wang1, Guopeng Wang2

  • 1State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China.

Nature Structural & Molecular Biology
|August 28, 2025
PubMed
Summary
This summary is machine-generated.

Researchers visualized the mitochondrial TOM-TIM23 supercomplex, revealing how proteins are sorted across mitochondrial membranes. This provides new insights into the mechanisms of mitochondrial protein import and sorting.

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Area of Science:

  • Mitochondrial biology
  • Molecular and structural biology

Background:

  • Protein import into mitochondria is essential for cellular function.
  • The mitochondrial translocase of the outer membrane (TOM) and translocase of the inner membrane 23 (TIM23) complexes mediate protein translocation across mitochondrial membranes.
  • The precise mechanisms of substrate recognition and sorting within the coupled TOM-TIM23 pathway are not fully understood.

Purpose of the Study:

  • To elucidate the structural mechanisms underlying protein recognition and sorting in the TOM-TIM23 pathway.
  • To visualize the dynamic interactions between a translocating polypeptide and the TOM-TIM23 supercomplex.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) was used to determine the structures of the TOM-TIM23 supercomplex with a translocating polypeptide substrate.
  • Structural analysis focused on the conformations of the polypeptide and its interactions with TOM and TIM23 complex subunits.

Main Results:

  • The study captured multiple conformations of a polypeptide substrate within the TOM complex, stabilized by hydrophilic residues of the Tom40 channel.
  • The TIM23 complex translocation pathway involves Tim17 and Mgr2 subunits, featuring a hydrophobic constriction regulated by substrate hydrophobicity.
  • Substrate hydrophobicity dynamically modulates Mgr2-Tim17 association, controlling protein sorting to the mitochondrial matrix or membrane.

Conclusions:

  • The findings reveal a sophisticated translocation mechanism within the TOM-TIM23 supercomplex.
  • This mechanism ensures efficient and regulated import of diverse mitochondrial proteins.
  • The structural insights provide a foundation for understanding mitochondrial protein import disorders.