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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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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...
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Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

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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...
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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
Cotranslational Protein Translocation01:20

Cotranslational Protein Translocation

7.6K
Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
7.6K
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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Related Experiment Video

Updated: Sep 11, 2025

Measurement of Protein Import Capacity of Skeletal Muscle Mitochondria
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Principles of cotranslational mitochondrial protein import.

Zikun Zhu1, Saurav Mallik2, Taylor A Stevens1

  • 1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

Cell
|August 12, 2025
PubMed
Summary

Nearly 20% of mitochondrial proteins are imported into mitochondria cotranslationally in human cells. This pathway, requiring a presequence, enhances the import of complex proteins by localizing translation to the mitochondrial surface.

Keywords:
NACTOM complexcotranslational protein importlocalized translationmitochondriamitochondrial targeting sequencenascent polypeptide-associated complexprotein foldingprotein targetingribosome profiling

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Mitochondrial Biology

Background:

  • Most mitochondrial proteins are synthesized on cytosolic ribosomes.
  • The precise mechanisms for delivering these proteins to mitochondria are not fully understood.

Purpose of the Study:

  • To investigate the extent and mechanisms of cotranslational protein import into mitochondria.
  • To identify the characteristics of proteins targeted via this pathway.

Main Methods:

  • Selective ribosome profiling in human cells.
  • Analysis of protein presequences and targeting efficiency.

Main Results:

  • Approximately 20% of mitochondrial proteins are imported cotranslationally.
  • Cotranslational import requires an N-terminal presequence and occurs at the mitochondrial surface.
  • This pathway preferentially targets large, multi-domain proteins, enhancing their import efficiency.
  • Mitochondrial presequences delay targeting until a significant protein domain is synthesized, unlike ER targeting.

Conclusions:

  • A significant proportion of mitochondrial proteins utilize cotranslational import.
  • This pathway involves a regulated targeting mechanism ensuring efficient delivery of complex proteins.
  • Mitochondrial protein sorting employs a sophisticated, multi-layered strategy for timing and specificity.